Skip to main content
SpringerLink
Log in

P2 purinergic receptors regulate the progression of colorectal cancer

  • Review
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

A Correction to this article was published on 01 March 2024

This article has been updated

Abstract

More and more studies have revealed that P2 purinergic receptors play a key role in the progression of colorectal cancer (CRC). P2X and P2Y purinergic receptors can be used as promoters and regulators of CRC and play a dual role in the progression of CRC. CRC microenvironment is rich in ATP and its cleavage products (ADP, AMP, Ado), which act as activators of P2X and P2Y purinergic receptors. The activation of P2X and P2Y purinergic receptors regulates the progression of CRC mainly by regulating the function of immune cells and mediating different signal pathways. In this paper, we focus on the specific mechanisms and functional roles of P2X7, P2Y12, and P2Y2 receptors in the growth and progression of CRC. The antagonistic effects of these selective antagonists of P2X purinergic receptors on the growth, invasion, and metastasis of CRC were further discussed. Moreover, different studies have reported that P2X7 receptor can be used as an effective predictor of patients with CRC. All these indicate that P2 purinergic receptors are a key regulator of CRC. Therefore, antagonizing P2 purinergic receptors may be an innovative treatment for CRC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this article. And we have not used other data that has already been published. All the data presented in this article are original results derived from this study.

Availability of supporting data

All data generated or analyzed during this study are included in this article, and we have not used other data that has already been published. All the data presented in this article are original results derived from this study.

Change history

References

  1. Li J, Ma X, Chakravarti D, Shalapour S, DePinho RA (2021) Genetic and biological hallmarks of colorectal cancer. Genes Dev 35(11–12):787–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sedlak JC, Yilmaz ÖH, Roper J (2023) Metabolism and colorectal cancer. Annu Rev Pathol 24(18):467–492

    Article  Google Scholar 

  3. Vultaggio-Poma V, Sarti AC, Di Virgilio F (2020) Extracellular ATP: a feasible target for cancer therapy. Cells 9(11):2496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yegutkin GG, Boison D (2022) ATP and adenosine metabolism in cancer: exploitation for therapeutic gain. Pharmacol Rev 74(3):797–822

    Article  PubMed  Google Scholar 

  5. Di Virgilio F, Sarti AC, Falzoni S, De Marchi E, Adinolfi E (2018) Extracellular ATP and P2 purinergic signalling in the tumour microenvironment. Nat Rev Cancer 18(10):601–618

    Article  PubMed  Google Scholar 

  6. Roliano GG, Azambuja JH, Brunetto VT, Butterfield HE, Kalil AN, Braganhol E (2022) Colorectal cancer and purinergic signalling: an overview. Cancers (Basel) 14(19):4887

    Article  CAS  PubMed  Google Scholar 

  7. Gendron FP, Placet M, Arguin G (2017) P2Y2 receptor functions in cancer: a perspective in the context of colorectal cancer. Adv Exp Med Biol 1051:91–106

    Article  CAS  PubMed  Google Scholar 

  8. Zhang WJ (2021) Effect of P2X purinergic receptors in tumor progression and as a potential target for anti-tumor therapy. Purinergic Signal 17(1):151–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Di Virgilio F, Falzoni S, Giuliani AL, Adinolfi E (2016) P2 receptors in cancer progression and metastatic spreading. Curr Opin Pharmacol 29:17–25

    Article  PubMed  Google Scholar 

  10. Bernardazzi C, Castelo-Branco MTL, Pêgo B, Ribeiro BE, Rosas SLB, Santana PT, Machado JC, Leal C, Thompson F, Coutinho-Silva R, de Souza HSP (2022) The P2X7 receptor promotes colorectal inflammation and tumorigenesis by modulating gut microbiota and the inflammasome. Int J Mol Sci 23(9):4616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Künzli BM, Bernlochner MI, Rath S, Käser S, Csizmadia E, Enjyoji K, Cowan P, d’Apice A, Dwyer K, Rosenberg R, Perren A, Friess H, Maurer CA, Robson SC (2011) Impact of CD39 and purinergic signalling on the growth and metastasis of colorectal cancer. Purinergic Signal 7(2):231–241

    Article  PubMed  PubMed Central  Google Scholar 

  12. Arneth B (2019) Tumor Microenvironment. Medicina (Kaunas) 56(1):15

    Article  PubMed  Google Scholar 

  13. Zhang WJ, Hu CG, Zhu ZM, Luo HL (2020) Effect of P2X7 receptor on tumorigenesis and its pharmacological properties. Biomed Pharmacother 125:109844

    Article  CAS  PubMed  Google Scholar 

  14. Han S, Wang W, Wang S, Yang T, Zhang G, Wang D, Ju R, Lu Y, Wang H, Wang L (2021) Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes. Theranostics 11(6):2892–2916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Alvarez CL, Troncoso MF, Espelt MV (2022) Extracellular ATP and adenosine in tumor microenvironment: roles in epithelial-mesenchymal transition, cell migration, and invasion. J Cell Physiol 237(1):389–400

    Article  CAS  PubMed  Google Scholar 

  16. Luo Y, Qiao B, Zhang P, Yang C, Cao J, Yuan X, Ran H, Wang Z, Hao L, Cao Y, Ren J, Zhou Z (2020) TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy. Theranostics 10(15):6987–7001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ge Q, Jia D, Cen D, Qi Y, Shi C, Li J, Sang L, Yang LJ, He J, Lin A, Chen S, Wang L (2021) Micropeptide ASAP encoded by LINC00467 promotes colorectal cancer progression by directly modulating ATP synthase activity. J Clin Invest 131(22):e152911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Qian Y, Wang X, Liu Y, Li Y, Colvin RA, Tong L, Wu S, Chen X (2014) Extracellular ATP is internalized by macropinocytosis and induces intracellular ATP increase and drug resistance in cancer cells. Cancer Lett 351(2):242–251

    Article  CAS  PubMed  Google Scholar 

  19. Wang X, Li Y, Qian Y, Cao Y, Shriwas P, Zhang H, Chen X (2017) Extracellular ATP, as an energy and phosphorylating molecule, induces different types of drug resistances in cancer cells through ATP internalization and intracellular ATP level increase. Oncotarget 8(50):87860–87877

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sameiyan E, Bagheri E, Dehghani S, Ramezani M, Alibolandi M, Abnous K, Taghdisi SM (2021) Aptamer-based ATP-responsive delivery systems for cancer diagnosis and treatment. Acta Biomater 15(123):110–122

    Article  Google Scholar 

  21. Zhang J, Wang Y, Chen J, Liang X, Han H, Yang Y, Li Q, Wang Y (2017) Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA. Int J Nanomedicine 3(12):4721–4732

    Article  Google Scholar 

  22. Kepp O, Bezu L, Yamazaki T, Di Virgilio F, Smyth MJ, Kroemer G, Galluzzi L (2021) ATP and cancer immunosurveillance. EMBO J 40(13):e108130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Feng LL, Cai YQ, Zhu MC, Xing LJ, Wang X (2020) The yin and yang functions of extracellular ATP and adenosine in tumor immunity. Cancer Cell Int 7(20):110

    Article  Google Scholar 

  24. Li XY, Moesta AK, Xiao C, Nakamura K, Casey M, Zhang H, Madore J, Lepletier A, Aguilera AR, Sundarrajan A, Jacoberger-Foissac C, Wong C, Dela Cruz T, Welch M, Lerner AG, Spatola BN, Soros VB, Corbin J, Anderson AC, Effern M, Hölzel M, Robson SC, Johnston RL, Waddell N, Smith C, Bald T, Geetha N, Beers C, Teng MWL, Smyth MJ (2019) Targeting CD39 in cancer reveals an extracellular ATP- and inflammasome-driven tumor immunity. Cancer Discov 9(12):1754–1773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xia C, Yin S, To KKW, Fu L (2023) CD39/CD73/A2AR pathway and cancer immunotherapy. Mol Cancer 22(1):44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lu JC, Zhang PF, Huang XY, Guo XJ, Gao C, Zeng HY, Zheng YM, Wang SW, Cai JB, Sun QM, Shi YH, Zhou J, Ke AW, Shi GM, Fan J (2021) Amplification of spatially isolated adenosine pathway by tumor-macrophage interaction induces anti-PD1 resistance in hepatocellular carcinoma. J Hematol Oncol 14(1):200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yang R, Elsaadi S, Misund K, Abdollahi P, Vandsemb EN, Moen SH, Kusnierczyk A, Slupphaug G, Standal T, Waage A, Slørdahl TS, Rø TB, Rustad E, Sundan A, Hay C, Cooper Z, Schuller AG, Woessner R, Borodovsky A, Menu E, Børset M, Sponaas AM (2020) Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade. J Immunother Cancer 8(1):e000610

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mao C, Yeh S, Fu J, Porosnicu M, Thomas A, Kucera GL, Votanopoulos KI, Tian S, Ming X (2022) Delivery of an ectonucleotidase inhibitor with ROS-responsive nanoparticles overcomes adenosine-mediated cancer immunosuppression. Sci Transl Med 14(648):eabh1261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Overes IM, Levenga TH, Vos JC, van Horssen-Zoetbrood A, van der Voort R, De Mulder PH, de Witte TM, Dolstra H (2009) Aberrant expression of the hematopoietic-restricted minor histocompatibility antigen LRH-1 on solid tumors results in efficient cytotoxic T cell-mediated lysis. Cancer Immunol Immunother 58(3):429–439

    Article  CAS  PubMed  Google Scholar 

  30. Wang K, Fu S, Dong L, Zhang D, Wang M, Wu X, Shen E, Luo L, Li C, Nice EC, Huang C, Zou B (2023) Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy. Autophagy 23:1–19

    Google Scholar 

  31. Cortier M, Boina-Ali R, Racoeur C, Paul C, Solary E, Jeannin JF, Bettaieb A (2015) H89 enhances the sensitivity of cancer cells to glyceryl trinitrate through a purinergic receptor-dependent pathway. Oncotarget 6(9):6877–6886

    Article  PubMed  PubMed Central  Google Scholar 

  32. Höpfner M, Lemmer K, Jansen A, Hanski C, Riecken EO, Gavish M, Mann B, Buhr H, Glassmeier G, Scherübl H (1998) Expression of functional P2-purinergic receptors in primary cultures of human colorectal carcinoma cells. Biochem Biophys Res Commun 251(3):811–817

    Article  PubMed  Google Scholar 

  33. Correale P, Tagliaferri P, Guarrasi R, Caraglia M, Giuliano M, Marinetti MR, Bianco AR, Procopio A (1997) Extracellular adenosine 5’ triphosphate involvement in the death of LAK-engaged human tumor cells via P2X-receptor activation. Immunol Lett 55(2):69–78

    Article  CAS  PubMed  Google Scholar 

  34. Zhang Y, Li F, Wang L, Lou Y (2021) A438079 affects colorectal cancer cell proliferation, migration, apoptosis, and pyroptosis by inhibiting the P2X7 receptor. Biochem Biophys Res Commun 18(558):147–153

    Article  Google Scholar 

  35. Zhang WJ, Luo C, Huang C, Pu FQ, Zhu JF, Zhu ZM (2021) PI3K/Akt/GSK-3β signal pathway is involved in P2X7 receptor-induced proliferation and EMT of colorectal cancer cells. Eur J Pharmacol 15(899):174041

    Article  Google Scholar 

  36. Zhang Y, Ding J, Wang L (2019) The role of P2X7 receptor in prognosis and metastasis of colorectal cancer. Adv Med Sci 64(2):388–394

    Article  PubMed  Google Scholar 

  37. Qian F, Xiao J, Hu B, Sun N, Yin W, Zhu J (2017) High expression of P2X7R is an independent postoperative indicator of poor prognosis in colorectal cancer. Hum Pathol 64:61–68

    Article  CAS  PubMed  Google Scholar 

  38. Calik I, Calik M, Turken G, Ozercan IH (2020) A promising independent prognostic biomarker in colorectal cancer: P2X7 receptor. Int J Clin Exp Pathol 13(2):107–121

    PubMed  PubMed Central  Google Scholar 

  39. Dillard C, Borde C, Mohammad A, Puchois V, Jourdren L, Larsen AK, Sabbah M, Maréchal V, Escargueil AE, Pramil E (2021) Expression pattern of purinergic signaling components in colorectal cancer cells and differential cellular outcomes induced by extracellular ATP and adenosine. Int J Mol Sci 22(21):11472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bellefeuille SD, Molle CM, Gendron FP (2019) Reviewing the role of P2Y receptors in specific gastrointestinal cancers. Purinergic Signal 15(4):451–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Delbro DS, Nylund G, Nordgren S (2005) Demonstration of P2Y4 purinergic receptors in the HT-29 human colon cancer cell line. Auton Autacoid Pharmacol 25(4):163–166

    Article  CAS  PubMed  Google Scholar 

  42. Schneider R, Leven P, Glowka T, Kuzmanov I, Lysson M, Schneiker B, Miesen A, Baqi Y, Spanier C, Grants I, Mazzotta E, Villalobos-Hernandez E, Kalff JC, Müller CE, Christofi FL, Wehner S (2021) A novel P2X2-dependent purinergic mechanism of enteric gliosis in intestinal inflammation. EMBO Mol Med 13(1):e12724

    Article  CAS  PubMed  Google Scholar 

  43. Nylund G, Nordgren S, Delbro DS (2004) Expression of P2Y2 purinoceptors in MCG 101 murine sarcoma cells, and HT-29 human colon carcinoma cells. Auton Neurosci 112(1–2):69–79

    Article  CAS  PubMed  Google Scholar 

  44. Nylund G, Hultman L, Nordgren S, Delbro DS (2007) P2Y2- and P2Y4 purinergic receptors are over-expressed in human colon cancer. Auton Autacoid Pharmacol 27(2):79–84

    Article  CAS  PubMed  Google Scholar 

  45. Di Virgilio F, Adinolfi E (2017) Extracellular purines, purinergic receptors and tumor growth. Oncogene 36(3):293–303

    Article  PubMed  Google Scholar 

  46. Song S, Jacobson KN, McDermott KM, Reddy SP, Cress AE, Tang H, Dudek SM, Black SM, Garcia JG, Makino A, Yuan JX (2016) ATP promotes cell survival via regulation of cytosolic [Ca2+] and Bcl-2/Bax ratio in lung cancer cells. Am J Physiol Cell Physiol 310(2):C99-

    Article  PubMed  Google Scholar 

  47. Zhang WJ, Hu CG, Luo HL, Zhu ZM (2020) Activation of P2×7 receptor promotes the invasion and migration of colon cancer cells via the STAT3 signaling. Front Cell Dev Biol 24(8):586555

    Article  Google Scholar 

  48. Erb L, Weisman GA (2012) Coupling of P2Y receptors to G proteins and other signaling pathways. Wiley Interdiscip Rev Membr Transp Signal 1(6):789–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. von Kügelgen I (2021) Molecular pharmacology of P2Y receptor subtypes. Biochem Pharmacol 187:114361

    Article  Google Scholar 

  50. Höpfner M, Maaser K, Barthel B, von Lampe B, Hanski C, Riecken EO, Zeitz M, Scherübl H (2001) Growth inhibition and apoptosis induced by P2Y2 receptors in human colorectal carcinoma cells: involvement of intracellular calcium and cyclic adenosine monophosphate. Int J Colorectal Dis 16(3):154–166

    Article  PubMed  Google Scholar 

  51. Girard M, Dagenais Bellefeuille S, Eiselt É, Brouillette R, Placet M, Arguin G, Longpré JM, Sarret P, Gendron FP (2020) The P2Y6 receptor signals through Gαq /Ca2+ /PKCα and Gα13/ROCK pathways to drive the formation of membrane protrusions and dictate cell migration. J Cell Physiol 235(12):9676–9690

    Article  CAS  PubMed  Google Scholar 

  52. Shawki S, Ashburn J, Signs SA, Huang E (2018) Colon cancer: inflammation-associated cancer. Surg Oncol Clin N Am 27(2):269–287

    Article  PubMed  Google Scholar 

  53. Rotondo JC, Mazziotta C, Lanzillotti C, Stefani C, Badiale G, Campione G, Martini F, Tognon M (2022) The role of purinergic P2X7 receptor in inflammation and cancer: novel molecular insights and clinical applications. Cancers (Basel) 14(5):1116

    Article  CAS  PubMed  Google Scholar 

  54. Figliuolo VR, Savio LEB, Safya H, Nanini H, Bernardazzi C, Abalo A, de Souza HSP, Kanellopoulos J, Bobé P, Coutinho CMLM, Coutinho-Silva R (2017) P2X7 receptor promotes intestinal inflammation in chemically induced colitis and triggers death of mucosal regulatory T cells. Biochim Biophys Acta Mol Basis Dis 1863(6):1183–1194

    Article  CAS  PubMed  Google Scholar 

  55. Diezmos EF, Markus I, Perera DS, Gan S, Zhang L, Sandow SL, Bertrand PP, Liu L (2018) Blockade of pannexin-1 channels and purinergic P2X7 receptors shows protective effects against cytokines-induced colitis of human colonic mucosa. Front Pharmacol 6(9):865

    Article  Google Scholar 

  56. Hofman P, Cherfils-Vicini J, Bazin M, Ilie M, Juhel T, Hébuterne X, Gilson E, Schmid-Alliana A, Boyer O, Adriouch S, Vouret-Craviari V (2015) Genetic and pharmacological inactivation of the purinergic P2RX7 receptor dampens inflammation but increases tumor incidence in a mouse model of colitis-associated cancer. Cancer Res 75(5):835–845

    Article  CAS  PubMed  Google Scholar 

  57. Kurashima Y, Amiya T, Nochi T, Fujisawa K, Haraguchi T, Iba H, Tsutsui H, Sato S, Nakajima S, Iijima H, Kubo M, Kunisawa J, Kiyono H (2012) Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors. Nat Commun 3:1034

    Article  ADS  PubMed  Google Scholar 

  58. Wang X, Yuan X, Su Y, Hu J, Ji Q, Fu S, Li R, Hu L, Dai C (2021) Targeting purinergic receptor P2RX1 modulates intestinal microbiota and alleviates inflammation in colitis. Front Immunol 20(12):696766

    Article  Google Scholar 

  59. Zhong P, Wu H, Ma Y, Xu X, Jiang Y, Jin C, Zhu Q, Liu X, Suo Z, Wang J (2023) P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis. Clin Transl Med 13(4):e1227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ghanawat M, Arjmand B, Rahim F (2023) The pro-tumor and anti-tumor effects of NLRP3 inflammasome as a new therapeutic option for colon cancer: a meta-analysis of pre-clinical studies. J Gastrointest Cancer 54(1):227–236

    Article  CAS  PubMed  Google Scholar 

  61. Saber S, Youssef ME, Sharaf H, Amin NA, El-Shedody R, Aboutouk FH, El-Galeel YA, El-Hefnawy A, Shabaka D, Khalifa A, Saleh RA, Osama D, El-Zoghby G, Gobba NA (2021) BBG enhances OLT1177-induced NLRP3 inflammasome inactivation by targeting P2X7R/NLRP3 and MyD88/NF-κB signaling in DSS-induced colitis in rats. Life Sci 1(270):119123

    Article  Google Scholar 

  62. Zhang J, Wang XJ, Wu LJ, Yang L, Yang YT, Zhang D, Hong J, Li XY, Dong XQ, Guo XC, Han R, Ma X (2021) Herb-partitioned moxibustion alleviates colonic inflammation in Crohn’s disease rats by inhibiting hyperactivation of the NLRP3 inflammasome via regulation of the P2X7R-Pannexin-1 signaling pathway. PLoS One 16(5):e0252334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Solini A, Cobuccio L, Rossi C, Parolini F, Biancalana E, Cosio S, Chiarugi M, Gadducci A (2022) Molecular characterization of peritoneal involvement in primary colon and ovary neoplasm: the possible clinical meaning of the P2X7 receptor-inflammasome complex. Eur Surg Res 63(3):114–122

    Article  CAS  PubMed  Google Scholar 

  64. Janakiram NB, Mohammed A, Bryant T, Brewer M, Biddick L, Lightfoot S, Lang ML, Rao CV (2015) Adoptive transfer of regulatory T cells promotes intestinal tumorigenesis and is associated with decreased NK cells and IL-22 binding protein. Mol Carcinog 54(10):986–998

    Article  CAS  PubMed  Google Scholar 

  65. Yang C, Shi S, Su Y, Tong JS, Li L (2020) P2X7R promotes angiogenesis and tumour-associated macrophage recruitment by regulating the NF-κB signalling pathway in colorectal cancer cells. J Cell Mol Med 24(18):10830–10841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ding C, Li L, Yang T, Fan X, Wu G (2016) Combined application of anti-VEGF and anti-EGFR attenuates the growth and angiogenesis of colorectal cancer mainly through suppressing AKT and ERK signaling in mice model. BMC Cancer 16(1):791

    Article  PubMed  PubMed Central  Google Scholar 

  67. de Andrade MP, Bian S, Savio LEB, Zhang H, Zhang J, Junger W, Wink MR, Lenz G, Buffon A, Wu Y, Robson SC (2017) Hyperthermia and associated changes in membrane fluidity potentiate P2X7 activation to promote tumor cell death. Oncotarget 8(40):67254–67268

    Article  Google Scholar 

  68. Adinolfi E, Capece M, Franceschini A, Falzoni S, Giuliani AL, Rotondo A, Sarti AC, Bonora M, Syberg S, Corigliano D, Pinton P, Jorgensen NR, Abelli L, Emionite L, Raffaghello L, Pistoia V, Di Virgilio F (2015) Accelerated tumor progression in mice lacking the ATP receptor P2X7. Cancer Res 75(4):635–644

    Article  CAS  PubMed  Google Scholar 

  69. Selzner N, Selzner M, Graf R, Ungethuem U, Fitz JG, Clavien PA (2004) Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding. Cell Death Differ 11(Suppl 2):S172–S180

    Article  CAS  PubMed  Google Scholar 

  70. Gao P, He M, Zhang C, Geng C (2018) Integrated analysis of gene expression signatures associated with colon cancer from three datasets. Gene 15(654):95–102

    Article  Google Scholar 

  71. Schmitt M, Ceteci F, Gupta J, Pesic M, Böttger TW, Nicolas AM, Kennel KB, Engel E, Schewe M, Callak Kirisözü A, Petrocelli V, Dabiri Y, Varga J, Ramakrishnan M, Karimova M, Ablasser A, Sato T, Arkan MC, de Sauvage FJ, Greten FR (2022) Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation. Nature 612(7939):347–353

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  72. Qin J, Zhang X, Tan B, Zhang S, Yin C, Xue Q, Zhang Z, Ren H, Chen J, Liu M, Qian M, Du B (2020) Blocking P2X7-mediated macrophage polarization overcomes treatment resistance in lung cancer. Cancer Immunol Res 8(11):1426–1439

    Article  CAS  PubMed  Google Scholar 

  73. Qiao C, Tang Y, Li Q, Zhu X, Peng X, Zhao R (2022) ATP-gated P2X7 receptor as a potential target for prostate cancer. Hum Cell 35(5):1346–1354

    Article  CAS  PubMed  Google Scholar 

  74. Mohammed A, Janakiram NB, Madka V, Pathuri G, Li Q, Ritchie R, Biddick L, Kutche H, Zhang Y, Singh A, Gali H, Lightfoot S, Steele VE, Suen CS, Rao CV (2017) Lack of chemopreventive effects of P2X7R inhibitors against pancreatic cancer. Oncotarget 8(58):97822–97834

    Article  PubMed  PubMed Central  Google Scholar 

  75. Sougiannis AT, VanderVeen B, Chatzistamou I, Kubinak JL, Nagarkatti M, Fan D, Murphy EA (2022) Emodin reduces tumor burden by diminishing M2-like macrophages in colorectal cancer. Am J Physiol Gastrointest Liver Physiol 322(3):G383–G395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Limami Y, Pinon A, Leger DY, Pinault E, Delage C, Beneytout JL, Simon A, Liagre B (2012) The P2Y2/Src/p38/COX-2 pathway is involved in the resistance to ursolic acid-induced apoptosis in colorectal and prostate cancer cells. Biochimie 94(8):1754–1763

    Article  CAS  PubMed  Google Scholar 

  77. Placet M, Arguin G, Molle CM, Babeu JP, Jones C, Carrier JC, Robaye B, Geha S, Boudreau F, Gendron FP (2018) The G protein-coupled P2Y6 receptor promotes colorectal cancer tumorigenesis by inhibiting apoptosis. Biochim Biophys Acta Mol Basis Dis 1864(5 Pt A):1539–1551

    Article  CAS  PubMed  Google Scholar 

  78. Xu XR, Yousef GM, Ni H (2018) Cancer and platelet crosstalk: opportunities and challenges for aspirin and other antiplatelet agents. Blood 131(16):1777–1789

    Article  CAS  PubMed  Google Scholar 

  79. Plantureux L, Mège D, Crescence L, Carminita E, Robert S, Cointe S, Brouilly N, Ezzedine W, Dignat-George F, Dubois C, Panicot-Dubois L (2020) The interaction of platelets with colorectal cancer cells inhibits tumor growth but promotes metastasis. Cancer Res 80(2):291–303

    Article  CAS  PubMed  Google Scholar 

  80. Mammadova-Bach E, Gil-Pulido J, Sarukhanyan E, Burkard P, Shityakov S, Schonhart C, Stegner D, Remer K, Nurden P, Nurden AT, Dandekar T, Nehez L, Dank M, Braun A, Mezzano D, Abrams SI, Nieswandt B (2020) Platelet glycoprotein VI promotes metastasis through interaction with cancer cell-derived galectin-3. Blood 135(14):1146–1160

    PubMed  Google Scholar 

  81. Hu JL, Zhang WJ (2023) The role and pharmacological properties of P2Y12 receptor in cancer and cancer pain. Biomed Pharmacother 157:113927

    Article  CAS  PubMed  Google Scholar 

  82. Palacios-Acedo AL, Mezouar S, Mège D, Crescence L, Dubois C, Panicot-Dubois L (2021) P2RY12-inhibitors reduce cancer-associated thrombosis and tumor growth in pancreatic cancers. Front Oncol 13(11):704945

    Article  Google Scholar 

  83. Ballerini P, Dovizio M, Bruno A, Tacconelli S, Patrignani P (2018) P2Y12 receptors in tumorigenesis and metastasis. Front Pharmacol 2(9):66

    Article  Google Scholar 

  84. Zarà M, Canobbio I, Visconte C, Canino J, Torti M, Guidetti GF (2018) Molecular mechanisms of platelet activation and aggregation induced by breast cancer cells. Cell Signal 48:45–53

    Article  PubMed  Google Scholar 

  85. Kim WT, Mun JY, Baek SW, Kim MH, Yang GE, Jeong MS, Choi SY, Han JY, Kim MH, Leem SH (2022) Secretory SERPINE1 Expression is increased by antiplatelet therapy, inducing MMP1 expression and increasing colon cancer metastasis. Int J Mol Sci 23(17):9596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wright JR, Chauhan M, Shah C, Ring A, Thomas AL, Goodall AH, Adlam D (2020) The TICONC (Ticagrelor-Oncology) study: implications of P2Y12 inhibition for metastasis and cancer-associated thrombosis. JACC CardioOncol 2(2):236–250

    Article  PubMed  PubMed Central  Google Scholar 

  87. Guillem-Llobat P, Dovizio M, Bruno A, Ricciotti E, Cufino V, Sacco A, Grande R, Alberti S, Arena V, Cirillo M, Patrono C, FitzGerald GA, Steinhilber D, Sgambato A, Patrignani P (2016) Aspirin prevents colorectal cancer metastasis in mice by splitting the crosstalk between platelets and tumor cells. Oncotarget 7(22):32462–32477

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

These studies were supported by grants from the Youth Science Foundation of Jiangxi Province (20224BAB216030), the Project of Education Department of Jiangxi Province (GJJ2200238), the Natural Science Foundation of Jiangxi Province (20232BAB206048), and the Jiangxi Province Traditional Chinese Medicine Science and Technology Plan (2023B1213).

Author information

Authors and Affiliations

  1. Department of Rehabilitation Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang City, 343000, Jiangxi Province, China

    Wen-jun Zhang, Si-jian Lin & Cheng-yi Wang

  2. Gastrointestinal Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang City, 343000, Jiangxi Province, China

    Li-peng Zhang & Yi-guan Le

Authors
  1. Wen-jun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li-peng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Si-jian Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cheng-yi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi-guan Le
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Wen-jun Zhang: Completed the writing and the final manuscript, reviewed and revised the article.

Li-peng Zhang: Completed the data collection and drafted the paper.

Si-jian Lin: Completed the review and revision.

Cheng-yi Wang: Complete the references and revision.

Yi-guan Le: Completed the revision and guidance.

Corresponding author

Correspondence to Yi-guan Le.

Ethics declarations

Competing interests

The authors declare no competing interests.

Conflict of interest

Wen-jun Zhang declares that he/she has no conflict of interest.

Li-peng Zhang declares that he/she has no conflict of interest.

Si-jian Lin declares that he/she has no conflict of interest.

Cheng-yi Wang declares that he/she has no conflict of interest.

Yi-guan Le declares that he/she has no conflict of interest.

Ethical approval and consent to participate

Ethical approval has been exempted by the Ethics Committee of the Second Affiliate Hospital of Nanchang University. All protocols were approved by the Animal Care and Ethics Committee, China.

Consent for publication

Not applicable.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Wj., Zhang, Lp., Lin, Sj. et al. P2 purinergic receptors regulate the progression of colorectal cancer. Purinergic Signalling (2023). https://doi.org/10.1007/s11302-023-09983-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11302-023-09983-6

Keywords

Search

Navigation