Skip to main content

Advertisement

Springer Nature Link
Log in

SGK1, autophagy and cancer: an overview

  • Review
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

The serum and glucocorticoid-induced kinase-1 (SGK1) belonging to the AGC protein kinase family phosphorylates serine and threonine residues of target proteins. It regulates numerous ion channels and transporters and promotes survival under cellular stress. Unique to SGK1 is a tight control at transcriptional and post-transcriptional levels. SGK1 regulates multiple signal transduction pathways related to tumor development. Several studies have reported that SGK1 is upregulated in different types of human malignancies and induces resistance against inhibitors, drugs, and targeted therapies.

Results and Conclusion

This review highlights the cellular functions of SGK1, its crucial role in cancer development, and clinical insights for SGK1 targeted therapies. Furthermore, the role of SGK1-mediated autophagy as a potential therapeutic target for cancer has been discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

SGK:

Serum and glucocorticoid-induced kinase-1

AKT:

Protein kinase B

PKA:

CAMP dependent protein kinase

PDK1:

Phosphoinositide dependent protein kinase-1

PKG:

CGMP dependent protein kinase

S6K:

Ribosomal S6 kinase

PKC:

Protein kinase C

MAST:

Microtubule-associated serine/threonine kinase

ROCK:

Rho-associated protein kinase

YANK:

Yet another novel kinase

GRK:

G protein-coupled receptor kinase

Nt:

Amino-terminus

Ct:

Carboxy-terminus

ER:

Endoplasmic reticulum

PIP3 :

Phosphatidylinositol-trisphosphate

TGFβ:

Growth factor beta

FSH:

Follicle stimulating hormone

ENaC:

Epithelial sodium channel

Th1:

Type-1 T helper cells

Tregs:

Regulatory T cells

ECM:

Extra cellular matrix

TME:

Tumor microenvironment

mTORC1:

Mammalian target of rapamycin complex-1

YAP:

Yes-associated protein

GLI1:

GLI family zinc finger-1

MTA1:

Metastasis-associated protein-1

PIN1:

Peptidyl-prolyl cis/trans isomerase NIMA-interacting-1

TAMs:

Tumor-associated macrophages

APC:

Adenomatous polyposis coli

shRNA:

Short hairpin RNA

CMA:

Chaperone-mediated autophagy

LAMP2A:

Lysosomal-associated membrane protein-2A

LC3B2:

Microtubule-associated proteins 1A/1B light chain-3B2

FOXO3:

Forkhead box O3

ULK1:

Unc-51 like autophagy activating kinase-1

BECN1:

Beclin-1

References

  1. Engelman JA, Luo J, Cantley LC (2006) The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7:606–619. https://doi.org/10.1038/nrg1879

    Article  CAS  PubMed  Google Scholar 

  2. Samuels Y, Zhenghe W, Alberto B, Natalie S, Janine P, Steve S, Hai Y, Adi G, Steven MP, Gregory JR (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304:554. https://doi.org/10.1126/science.1096502

    Article  CAS  PubMed  Google Scholar 

  3. Fruman DA, Honyin C, Benjamin DH, Shubha B, Lewis CC, Robert TA (2017) The PI3K pathway in human disease. Cell 170:605–635. https://doi.org/10.1016/j.cell.2017.07.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kondapalli L, Soltani K, Lacouture ME (2005) The promise of molecular targeted therapies: protein kinase inhibitors in the treatment of cutaneous malignancies. J Am Acad Dermatol 53:291–302. https://doi.org/10.1016/j.jaad.2005.02.011

    Article  PubMed  Google Scholar 

  5. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298:1912–1934. https://doi.org/10.1126/science.1075762

    Article  CAS  PubMed  Google Scholar 

  6. Maurer M (2009) 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma. Cancer Res 69:6299–6306. https://doi.org/10.1158/0008-5472.CAN-09-0820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kobayashi T, Deak M, Morrice N, Cohen P (1999) Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem J 344:189–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Webster MK, Goya L, Ge Y, Maiyar AC, Firestone GL (1993) Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol Cell Biol 13:2031–2040. https://doi.org/10.1128/mcb.13.4.2031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Waldegger S, Barth P, Raber G, Lang F (1997) Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume. Proc Natl Acad Sci USA 94:4440–4445. https://doi.org/10.1073/pnas.94.9.4440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lang F, Bohmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V (2006) (Patho) physiological significance of the serum- and glucocorticoidinducible kinase isoforms. Physiol Rev 86:1151–1178. https://doi.org/10.1152/physrev.00050.2005

    Article  CAS  PubMed  Google Scholar 

  11. Rauz S, Walker EA, Hughes SV, Coca-Prados M, Hewison M, Murray PL, Stewart PM (2003) Serum- and glucocorticoid-regulated kinase isoform-1 and epithelial sodium channel subunits in human ocular ciliary epithelium. IOVS 44:1643–1651. https://doi.org/10.1167/iovs.02-0514

    Article  Google Scholar 

  12. Wang HW, Huang BS, Chen A, Ahmad M, White RA, Leenen FH (2016) Role of brain aldosterone and mineralocorticoid receptors in aldosterone-salt hypertension in rats. Neuroscience 314:90–105. https://doi.org/10.1016/j.neuroscience.2015.11.055

    Article  CAS  PubMed  Google Scholar 

  13. Sahin P, McCaig C, Jeevahan J, Murray JT, Hainsworth AH (2013) The cell survival kinase SGK1 and its targets FOXO3a and NDRG1 in aged human brain. Neuropathol Appl Neurobiol 39:623–633. https://doi.org/10.1111/nan.12023

    Article  CAS  PubMed  Google Scholar 

  14. Lee E, Lein ES, Firestone GL (2001) Tissue-specific expression of the transcriptionally regulated serum and glucocorticoid-inducible protein kinase (Sgk) during mouse embryogenesis. Mech Dev 103:177–181. https://doi.org/10.1016/s0925-4773(01)00351-3

    Article  CAS  PubMed  Google Scholar 

  15. Waldegger S, Klingel K, Barth P, Sauter M, Rfer ML, Kandolf R, Lang F (1999) h-sgk serine-threonine protein kinase gene as transcriptional target of transforming growth factor beta in human intestine. Gastroenterology 116(5):1081–1088. https://doi.org/10.1016/s0016-5085(99)70011-9

    Article  CAS  PubMed  Google Scholar 

  16. Yu XB, Lin Q, Qin X, Ruan Z, Zhou JH, Lin ZF, Su YJ, Jian Z (2016) Serum and glucocorticoid kinase 1 promoted the growth and migration of non-small cell lung cancer cells. Gene 576:339–346. https://doi.org/10.1016/j.gene.2015.10.072

    Article  CAS  Google Scholar 

  17. Yaylaoglu MB, Agbemafle BM, Oesterreicher TJ, Finegold MJ, Thaller C, Henning SJ (2006) Diverse patterns of cell-specific gene expression in response to glucocorticoid in the developing small intestine. Am J Physiol Gastrointest Liver Physiol 291:G1041–G1050. https://doi.org/10.1152/ajpgi.00139.2006

    Article  CAS  PubMed  Google Scholar 

  18. Hou JH, Speirs HJ, Seckl JR, Brown RW (2002) Sgk1 gene expression in kidney and its regulation by aldosterone: Spatio-temporal heterogeneity and quantitative analysis. J Am Soc Nephrol 13:1190–1198. https://doi.org/10.1097/01.ASN.0000013702.73570.3B

    Article  CAS  PubMed  Google Scholar 

  19. Klingel K, Warntges S, Bock J, Wagner CA, Sauter M, Waldegger S, Kandolf R, Lang F (2000) Expression of cell volume-regulated kinase h-sgk in pancreatic tissue. Am J Physiol Gastrointest Liver Physiol 279:G998–G1002. https://doi.org/10.1152/ajpgi.2000.279.5.G998

    Article  CAS  PubMed  Google Scholar 

  20. Murray JT, Campbell DG, Morrice N, Auld GC, Shpiro N, Marquez R, Peggie M, Bain J, Bloomberg GB, Grahammer F (2004) Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Biochem J 84:477–488. https://doi.org/10.1042/BJ20041057

    Article  Google Scholar 

  21. Chen L, Wei TQ, Wang Y, Zhang J, Li H, Wang KJ (2012) Simulated bladder pressure stimulates human bladder smooth muscle cell proliferation via the PI3K/SGK1 signaling pathway. J Urol 188:661–667. https://doi.org/10.1016/j.juro.2012.03.112

    Article  CAS  PubMed  Google Scholar 

  22. Li P, Pan F, Hao Y, Feng W, Song H, Zhu D (2013) SGK1 is regulated by metabolicrelated factors in 3T3-L1 adipocytes and overexpressed in the adipose tissue of subjects with obesity and diabetes. Diabetes Res Clin Pract 102:35–42. https://doi.org/10.1016/j.diabres.2013.08.009

    Article  CAS  PubMed  Google Scholar 

  23. Sun JY, Li C, Shen ZX, Zhang WC, Ai TJ, Du LJ, Zhang YY, Yao GF, Liu Y, Sun S (2016) Mineralocorticoid receptor deficiency in macrophages inhibits neointimal hyperplasia and suppresses macrophage inflammation through SGK1-AP1/NF-B pathways. Arterioscler Thromb Vasc Biol 36:874–885. https://doi.org/10.1161/ATVBAHA.115.307031

    Article  CAS  PubMed  Google Scholar 

  24. Pelzl L, Fakhri H, Umbach AT, Gawaz M, Paulmichl M, Lang F (2013) Sgk1 sensitive pendrin expression in murine platelets. Cell Physiol Biochem 32:210–220. https://doi.org/10.1159/000356640

    Article  CAS  PubMed  Google Scholar 

  25. Arteaga MF, Alvarez R, Alvar JA (2007) Multiple translational isoforms give functional specificity to serum- and glucocorticoid-induced kinase 1. Mol Biol Cell 18:2072–2080. https://doi.org/10.1091/mbc.E06-10-0968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bogusz MA, Brickley DR, Pew T, Conzen SD (2006) A novel N-terminal hydrophobic motif mediates constitutive degradation of serum and glucocorticoid-induced kinase-1 by the ubiquitin-proteasome pathway. FEBS J 273:2913–2928. https://doi.org/10.1111/j.1742-4658.2006.05304.x

    Article  CAS  PubMed  Google Scholar 

  27. Zhou R, Snyder PM (2005) Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradation. JBC 280:4518–4523. https://doi.org/10.1074/jbc.M411053200

    Article  CAS  Google Scholar 

  28. Pao AC (2012) SGK regulation of renal sodium transport. Curr Opin Nephrol Hypertens 2:534–540. https://doi.org/10.1097/MNH.0b013e32835571be

    Article  CAS  Google Scholar 

  29. Daniela R, Olivier S (2012) Nedd4-2 and the regulation of epithelial sodium transport. Front Physiol 3:212. https://doi.org/10.3389/fphys.2012.00212

    Article  Google Scholar 

  30. Yang N, Jiang J, Deng L, Waters MJ, Wang X, Frank SJ (2010) Growth hormone receptor targeting to lipid rafts requires extracellular subdomain 2. Biochem Biophys Res Commun 391:414–418. https://doi.org/10.1016/j.bbrc.2009.11.072

    Article  CAS  PubMed  Google Scholar 

  31. Diego AR, Ignacio G, Biff F, Cecilia MC (2006) SGK1 activates Na+-K+-ATPase in amphibian renal epithelial cells. AJP Cell Physiol 290(2):C492-498. https://doi.org/10.1152/ajpcell.00556.2004

    Article  CAS  Google Scholar 

  32. Du YN, Tang XF, Xu L, Chen WD, Gao PJ, Han WQ (2018) SGK1-FoxO1 signaling pathway mediates Th17/Treg imbalance and target organ inflammation in angiotensin II-induced hypertension. Front Physiol 9:1581. https://doi.org/10.3389/fphys.2018.01581

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wulff P, Vallon V, Huang DY, Volkl H, Yu F, Richter K, Jansen M, Schlunz M, Klingel K, Loffing J et al (2002) Impaired renal Na(+) retention in the sgk1-knockout mouse. J Clin Investig 110:1263–1268. https://doi.org/10.1172/JCI15696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sarah I, Shannon H, Philip V (2015) Serum- and glucocorticoid-inducible kinase 1 confers protection in cell-based and in in vivo neurotoxin models via the c-Jun N-terminal kinase signaling pathway. Mol Cell Biol 35:1192–2206. https://doi.org/10.1128/MCB.01510-14

    Article  CAS  Google Scholar 

  35. Ackermann TF, Boini KM, Beier N, Scholz W, Fuchss T, Lang F (2011) EMD638683, a novel SGK inhibitor with antihypertensive potency. Cell Physiol Biochem 28:137–146. https://doi.org/10.1159/000331722

    Article  CAS  PubMed  Google Scholar 

  36. Nishida Y, Nagata T, Takahashi Y, Sugahara-Kobayashi M, Murata A, Asai S (2004) Alteration of serum/glucocorticoid regulated kinase-1 (sgk-1) gene expression in rat hippocampus after transient global ischemia. Brain Res Mol Brain Res 123(1–2):121–125. https://doi.org/10.1016/j.molbrainres.2004.01.008

    Article  CAS  PubMed  Google Scholar 

  37. Zhuang X, Zhang H, Hu G (2019) Cancer and microenvironment plasticity: double-edged swords in metastasis. Trends Pharmacol Sci 40:419–429. https://doi.org/10.1016/j.tips.2019.04.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Conza D, Paola M, Gaetano TT, Luigi I, Francesca F, Silvia S, Rosario A, Francesco B, Nicola P et al (2017) The SGK1 inhibitor SI113 induces autophagy, apoptosis, and endoplasmic reticulum stress in endometrial cancer cells. J Cell Physiol 232(12):3735–3743. https://doi.org/10.1002/jcp.25850

    Article  CAS  PubMed  Google Scholar 

  39. Tian S, Wang X, Proud CG (2017) Oncogenic MNK signalling regulates the metastasis suppressor NDRG1. Oncotarget 8:46121–46135. https://doi.org/10.18632/oncotarget.17555

    Article  PubMed  PubMed Central  Google Scholar 

  40. Tang Z, Qin S, Hao X, Zhu Z, Guanglin S, Caixin Z, Anaz M, Yi W, Songshi N, Xiaoyu Z (2018) Serum and glucocorticoid-regulated kinase 1 (SGK1) is a predictor of poor prognosis in non-small cell lung cancer, and its dynamic pattern following treatment with SGK1 inhibitor and gamma-ray irradiation was elucidated. Oncol Rep 39:1505–1515. https://doi.org/10.3892/or.2018.6181

    Article  CAS  PubMed  Google Scholar 

  41. Wang K, Gu S, Nasir O, Foller M, Ackermann TF, Klingel K, Kandolf R, Kuhl D, Stournaras C, Lang F (2010) SGK1-dependent intestinal tumor growth in APC-deficient mice. Cell Physiol Biochem 25:271–278. https://doi.org/10.1159/000276561

    Article  CAS  PubMed  Google Scholar 

  42. Abbruzzese C, Mattarocci S, Pizzuti L, Mileo AM, Visca P, Antoniani B, Gabriele A, Francesco F, Rosario A, Lucia D et al (2012) Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas. J Exp Clin Cancer Res 31:1–4. https://doi.org/10.1186/1756-9966-31-4

    Article  CAS  Google Scholar 

  43. Chen X, Gu J, Wu Y, Liang P, Shen M, Xi J, Jian Q (2020) Clinical characteristics of colorectal cancer patients and anti-neoplasm activity of genistein. BioMed Pharmacother 124:109835. https://doi.org/10.1016/j.biopha.2020.109835

    Article  CAS  PubMed  Google Scholar 

  44. Feng Z, Liu L, Zhang C, Zheng T, Wang J, Lin M, Yuhan Z, Xiaowen W, Arnold JL, Wenwei H (2012) Chronic restraint stress attenuates p53 function and promotes tumorigenesis. Proc Natl Acad Sci USA 109:7013–7018. https://doi.org/10.1073/pnas.1203930109

    Article  PubMed  PubMed Central  Google Scholar 

  45. Naruse T, Yanamoto S, Okuyama K, Yamashita K, Omori K, Nakao Y, Shin-Ichi Y, Masahiro U (2017) Therapeutic implication of mTORC2 in oral squamous cell carcinoma. Oral Oncol 65:23–32. https://doi.org/10.1016/j.oraloncology.2016.12.012

    Article  CAS  PubMed  Google Scholar 

  46. Wu W, Zou M, Brickley DR, Pew T, Conzen SD (2006) Glucocorticoid receptor activation signals through forkhead transcription factor 3a in breast cancer cells. Mol Endocrinol 20:2304–2314. https://doi.org/10.1210/me.2006-0131

    Article  CAS  PubMed  Google Scholar 

  47. Zhang Z, Xu Q, Song C, Mi B, Zhang H, Kang H, Huiyong L, Yunlong S, Jia W, Zhuowei L et al (2020) Serum- and glucocorticoid-inducible kinase 1 is essential for osteoclastogenesis and promotes breast cancer bone metastasis. Mol Cancer Ther 19:650–660. https://doi.org/10.1158/1535-7163.MCT-18-0783

    Article  CAS  PubMed  Google Scholar 

  48. Szmulewitz RZ, Chung E, Al-Ahmadie H, Daniel S, Kocherginsky M, Razmaria A (2012) Serum/glucocorticoid-regulated kinase 1 expression in primary human prostate cancers. Prostate 72:157–164. https://doi.org/10.1002/pros.21416

    Article  CAS  PubMed  Google Scholar 

  49. Ronchi CL, Sbiera S, Leich E, Tissier F, Steinhauer S, Deutschbein T, Martin F, Bruno A (2012) Low SGK1 expression in human adrenocortical tumors is associated with ACTH-independent glucocorticoid secretion and poor prognosis. J Clin Endocrinol Metab 97(12):E2251–E2260. https://doi.org/10.1210/jc.2012-2669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sahoo S, Brickley DR, Kocherginsky M, Conzen SD (2005) Coordinate expressionbof the PI3-kinase downstream effectors serum and glucocorticoid-induced kinase (SGK-1) and Akt-1 in human breast cancer. Eur J Cancer 41:2754–2759. https://doi.org/10.1016/j.ejca.2005.07.018

    Article  CAS  PubMed  Google Scholar 

  51. Castel P, Haley E, Ruzica B, Eneda T, Pedram R, Javier C, Srinivasaraghavan K, Chandra SV, Maura D, Sarat C et al (2016) PDK1-SGK1 signaling sustains AKT-independent mTORC1 activation and confers resistance to PI3Kalpha inhibition. Cancer Cell 30:229–242. https://doi.org/10.1016/j.ccell.2016.06.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sommer EM, Dry H, Cross D, Guichard S, Davies BR, Alessi DR (2013) Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors. Biochem J 452:499–508. https://doi.org/10.1042/BJ20130342

    Article  CAS  PubMed  Google Scholar 

  53. Sherk AB, Frigo DE, Schnackenberg CG, Bray JD, Laping NJ, Trizna W (2008) Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer Res 68:7475–7483. https://doi.org/10.1158/0008-5472.CAN-08-1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Towhid ST, Liu GL, Ackermann TF, Beier N, Scholz W, Fuchß T, Mahmoud T, Hans-Peter R, Florian L (2013) Inhibition of colonic tumor growth by the selective SGK inhibitor EMD638683. Cell Physiol Biochem 32:838–848. https://doi.org/10.1159/000354486

    Article  CAS  PubMed  Google Scholar 

  55. Zhu J, Zhang R, Yang D, Li J, Yan X, Jin K, Li W, Liu X, Zhao J, Shang W et al (2018) Knockdown of long non-coding RNA XIST inhibited doxorubicin resistance in colorectal cancer by upregulation of miR-124 and downregulation of SGK1. Cell Physiol Biochem 51:113–128. https://doi.org/10.1159/000495168

    Article  CAS  PubMed  Google Scholar 

  56. D’Antona L, Dattilo V, Catalogna G, Scumaci D, Fiumara CV, Musumeci F, Giuseppe P, Silvia S, Rossana T, Cristina BS et al (2019) In preclinical model of ovarian cancer, the SGK1 inhibitor SI113 counteracts the development of paclitaxel resistance and restores drug sensitivity. Transl Oncol 12:1045–1055. https://doi.org/10.1016/j.tranon.2019.05.008

    Article  PubMed  PubMed Central  Google Scholar 

  57. Abbruzzese C, Matteoni S, Persico M, Ascione B, Schenone S, Musumeci F, Rosario A, Nicola P, Paola M, Marco GP et al (2019) The small molecule SI113 hinders epithelial-to-mesenchymal transition and subverts cytoskeletal organization in human cancer cells. J Cell Physiol 234:22529–22542. https://doi.org/10.1016/j.tranon.2019.05.008

    Article  CAS  PubMed  Google Scholar 

  58. Liang X, Chunling L, Jinzhe Z, Wencheng F, Xuesha L, Yu A, Guanming J, Kejin W, Yongqin L, Jiahong X (2017) Development of a new analog of SGK1 inhibitor and its evaluation as a therapeutic molecule of colorectal cancer. J Cancer 8:2256–2262. https://doi.org/10.7150/jca.19566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tangir J, Bonafe N, Gilmore-Hebert M, Henegariu O, Setsuko KC (2004) SGK1, a potential regulator of c-fms related breast cancer aggressiveness. Clin Exp Metastasis 21:477–483. https://doi.org/10.1007/s10585-004-4226-8

    Article  CAS  PubMed  Google Scholar 

  60. Fagerli UM, Ullrich K, Stuhmer T, Holien T, Kochert K, Holt RU, Bruland O, Chatterjee M, Nogai H, Lenz G et al (2011) Serum/glucocorticoid-regulated kinase 1 (SGK1) is a prominent target gene of the transcriptional response to cytokines in multiple myeloma and supports the growth of myeloma cells. Oncogene 30:3198–3206. https://doi.org/10.1038/onc.2011.79

    Article  CAS  PubMed  Google Scholar 

  61. Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, Green-Thompson ZW, Jimenez-Sanchez M, Korolchuk VI, Lichtenberg M, Luo S (2010) Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 90:1383–1435. https://doi.org/10.1152/physrev.00030.2009

    Article  CAS  PubMed  Google Scholar 

  62. Levine B, Klionsky DJ (2004) Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6:463–477. https://doi.org/10.1016/s1534-5807(04)00099-1

    Article  CAS  PubMed  Google Scholar 

  63. Saxton RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 169:361–371. https://doi.org/10.1016/j.cell.2017.02.004

    Article  CAS  PubMed  Google Scholar 

  64. Rabinowitz JD, White E (2010) Autophagy and metabolism. Science 330:1344–1348. https://doi.org/10.1126/science.1193497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jiao J, Demontis F (2017) Skeletal muscle autophagy and its role in sarcopenia and organismal aging. Curr Opin Pharmacol 34:1–6. https://doi.org/10.1016/j.coph.2017.03.009

    Article  CAS  PubMed  Google Scholar 

  66. Li WW, Li J, Bao JK (2012) Microautophagy: lesser-known self-eating. Cell Mol Life Sci 69:1125–1136. https://doi.org/10.1007/s00018-011-0865-5

    Article  CAS  PubMed  Google Scholar 

  67. Yu L, Chen Y, Tooze SA (2018) Autophagy pathway: cellular and molecular mechanisms. Autophagy 14:207–215. https://doi.org/10.1080/15548627.2017.1378838

    Article  CAS  PubMed  Google Scholar 

  68. Mizushima N (2018) A brief history of autophagy from cell biology to physiology and disease. Nat Cell Biol 20(5):521–527. https://doi.org/10.1038/s41556-018-0092-5

    Article  CAS  PubMed  Google Scholar 

  69. Sosa MS, Bragado P, Aguirre-Ghiso JA (2014) Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer 14(9):611–622. https://doi.org/10.1038/nrc3793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Luo L, Qin ZH (2019) Autophagy, aging, and longevity. Adv Exp Med Biol 1206:509–525. https://doi.org/10.1007/978-981-15-0602-4_24

    Article  CAS  PubMed  Google Scholar 

  71. Buytaert E, Callewaert G, Vandenheede JR, Agostinis P (2006) Deficiency in apoptotic effectors Bax and Bak reveals an autophagic cell death pathway initiated by photodamage to the endoplasmic reticulum. Autophagy 2:238–240. https://doi.org/10.4161/auto.2730

    Article  CAS  PubMed  Google Scholar 

  72. Bednarczyk M, Muc-Wierzgon M, Waniczek D, Fatyga E, Klakla K, Mazurek U, Wierzgon J (2017) Autophagy-related gene expression in colorectal cancer patients. J Biol Regul 31:923–927

    CAS  Google Scholar 

  73. Eissa S, Matboli M, Awad N, Kotb Y (2017) Identification and validation of a novel autophagy gene expression signature for human bladder cancer patients. Tumor Biol 39(4):1010428317698360. https://doi.org/10.1177/1010428317698360

    Article  CAS  Google Scholar 

  74. Xu CX, Zhao L, Yue P, Fang G, Tao H, Owonikoko TK, Ramalingam SS, Khuri FR, Sun SY (2011) Augmentation of NVP-BEZ235’s anticancer activity against human lung cancer cells by blockage of autophagy. Cancer Biol Ther 12(6):549–555. https://doi.org/10.4161/cbt.12.6.16397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yao Q, Chen J, Lv Y, Wang T, Zhang J, Fan J, Wang L (2011) The significance of expression of autophagy-related gene Beclin, Bcl-2, and Bax in breast cancer tissues. Tumor Biol 32(6):1163–1171. https://doi.org/10.1007/s13277-011-0219-9

    Article  CAS  Google Scholar 

  76. Saha S, Panigrahi DP, Patil S, Sujit KB (2018) Autophagy in health and disease: a comprehensive review. Biomed Pharmacother 104:485–495. https://doi.org/10.1016/j.biopha.2018.05.007

    Article  CAS  PubMed  Google Scholar 

  77. Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY, Bray K, Reddy A, Bhanot G, Gelinas C (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell 137:1062–1075. https://doi.org/10.1016/j.cell.2009.03.048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mathew R, White E (2011) Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr Opin Genet Dev 21:113–119. https://doi.org/10.1016/j.gde.2010.12.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402(6762):672–676. https://doi.org/10.1038/45257

    Article  CAS  PubMed  Google Scholar 

  80. Servante J, Estranero J, Meijer L, Layfield R, Grundy R (2018) Chemical modulation of autophagy as an adjunct to chemotherapy in childhood and adolescent brain tumors. Oncotarget 16:35266–35277. https://doi.org/10.18632/oncotarget.26186

    Article  Google Scholar 

  81. Sui X, Chen R, Wang Z, Huang Z, Kong N, Zhang M, Han W, Lou F, Yang J, Zhang Q, Wang X, He C, Pan H (2013) Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment. Cell Death Dis 4:e838. https://doi.org/10.1038/cddis.2013.350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Liu W, Xuchu W, Yiyun W, Yibei D, Yiyi X, Ying P, Binbin Y, Pan Y, Zhenping L, Xiuzhi D, Zhaoping L, Yuhua C, Chunhua L, Xiang L, Zhihua T (2018) SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT. J Exp Clin Cancer Res 37(1):73. https://doi.org/10.1186/s13046-018-0743-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Catalogna G, Talarico C, Dattilo V, Gangemi V, Calabria F, D’Antona L, Silvia S, Francesca M, Cataldo B, Nicola P et al (2017) The SGK1 kinase inhibitor SI113 sensitizes theranostic effects of the 64cucl2 in human glioblastoma multiforme cells. Cell Physiol Biochem 43:108–119. https://doi.org/10.1159/000480328

    Article  CAS  PubMed  Google Scholar 

  84. Zuleger T, Heinzelbecker J, Takacs Z, Catherine H, Jakob V, Florian L, Tassula PC (2018) SGK1 inhibits autophagy in murine muscle tissue. Oxid Med Cell Longev 2018:4043726. https://doi.org/10.1155/2018/4043726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Aspernig H, Heimbucher T, Qi W, Dipak G, Sedric C, Yijian Y, Erika DVG, Ralf B, Antje T (2019) Mitochondrial perturbations couple mTORC2 to autophagy in C. elegans. Cell Rep 29(6):399-1409.e5. https://doi.org/10.1016/j.celrep.2019.09.072

    Article  CAS  Google Scholar 

  86. Maestro I, Patricia B, Ana M (2020) Serum- and glucocorticoid-induced kinase 1, a new therapeutic target for autophagy modulation in chronic diseases. Expert Opin Ther Targets 24(3):231–243. https://doi.org/10.1080/14728222.2020.1730328

    Article  CAS  PubMed  Google Scholar 

  87. Talarico C, Dattilo V, D’Antona L, Barone A, Amodio N, Belviso S, Francesca M, Claudia A, Cataldo B, Francesco T et al (2016) SI113, a SGK1 inhibitor, potentiates the effects of radiotherapy, modulates the response to oxidative stress and induces cytotoxic autophagy in human glioblastoma multiforme cells. Oncotarget 7:15868–15884. https://doi.org/10.18632/oncotarget.7520

    Article  PubMed  PubMed Central  Google Scholar 

  88. Francipane MG, Lagasse E (2013) Selective targeting of human colon cancer stem-like cells by the mTOR inhibitor Torin-1. Oncotarget 4:1948–1962. https://doi.org/10.18632/oncotarget.1310

    Article  PubMed  PubMed Central  Google Scholar 

  89. Berdel HO, Yin H, Liu JY, Grochowska K, Middleton C, Yanasak N, Abdelsayed R, Berdel WE, Mozaffari M, Yu JC et al (2014) Targeting serum glucocorticoid-regulated kinase-1 in squamous cell carcinoma of the head and neck: a novel modality of local control. PLoS ONE 9:e113795. https://doi.org/10.1371/journal.pone.0113795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Singh PK, Singh S, Ganesh S (2013) Activation of serum/glucocorticoid-induced kinase 1 (SGK1) underlies increased glycogen levels, mTOR activation, and autophagy defects in Lafora disease. Mol Biol Cell 24:3776–3786. https://doi.org/10.1091/mbc.E13-05-0261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Andres-Mateos E, Brinkmeier H, Burks TN, Mejias R, Files DC, Steinberger M, Arshia S, Ruth M, Jessica LS, Benjamin L et al (2013) Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy. EMBO Mol Med 5:80–91. https://doi.org/10.1002/emmm.201201443

    Article  CAS  PubMed  Google Scholar 

  92. Sang Y, Kong P, Zhang S, Zhang L, Cao Y, Duan X, Sun T, Tao Z, Liu W (2021) SGK1 in human cancer: emerging roles and mechanisms. Front Oncol 10:608722. https://doi.org/10.3389/fonc.2020.608722

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Haidian District, Beijing, 100084, China

    Madiha Javeed Ghani

Authors
  1. Madiha Javeed Ghani
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

MJG conceptualized the study, searched the literature, drafted and reviewed the manuscript, and designed illustrations using BioRender tool.

Corresponding author

Correspondence to Madiha Javeed Ghani.

Ethics declarations

Conflict of interest

The author declares no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by the author.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghani, M.J. SGK1, autophagy and cancer: an overview. Mol Biol Rep 49, 675–685 (2022). https://doi.org/10.1007/s11033-021-06836-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06836-6

Keywords