Skip to main content

Advertisement

SpringerLink
Log in

Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of triple negative breast cancer cells

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

Triple negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis. The role of profilin 2 (PFN2) in TNBC is very controversial. The current study is to explore the role of PFN2 in TNBC.

Methods

PFN2 expression in TNBC and normal breast tissues were evaluated by immunohistochemical analysis. The association between PFN2 expression and prognosis in TNBC patients was analyzed from the TCGA database. A cell counting kit-8 (CCK8) assay was employed to investigate the effects of PFN2 in TNBC cell proliferations. The migration and invasion capability of TNBC cells was evaluated by transwell assays. Western blot was performed to assess the related protein expression of TGF-β/Smad signaling and epithelial to mesenchymal transition. Finally, TNBC xenografts were established to determine the tumorigenicity in vivo using female Nod/Scid mice.

Results

PFN2 is upregulated in TNBC and the higher expression was associated with worse survival. CCK8 assays and Transwell assays demonstrated that PFN2 promoted the proliferation, migration and invasion of TNBC cells. Smad2 and Smad3 were upregulated in PFN2 overexpressing TNBC cells, which further induced the process of epithelial‑to‑mesenchymal transition. Similarly, the overexpressing PFN2 TNBC cells exhibited stronger tumorigenicity in vivo.

Conclusions

Higher PFN2 expression is associated with a worse 10-year overall survival and relapse-free survival in breast cancer patients, as well as worse 10-year relapse-free survival in TNBC patients. PFN2 promotes the proliferation, migration and invasion of TNBC cells by regulating epithelial-to-mesenchymal transition.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363:1938–48.

    Article  CAS  Google Scholar 

  2. Li X, Yang J, Peng L, et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. 2017;161:279–87.

    Article  Google Scholar 

  3. Zeichner SB, Terawaki H, Gogineni K. A review of systemic treatment in metastatic triple-negative breast cancer. Breast Cancer (Auckl). 2016;10:25–36.

    CAS  Google Scholar 

  4. Li Y, Grenklo S, Higgins T, et al. The profilin:actin complex localizes to sites of dynamic actin polymerization at the leading edge of migrating cells and pathogen-induced actin tails. Eur J Cell Biol. 2008;87:893–904.

    Article  CAS  Google Scholar 

  5. Yan J, Ma C, Gao Y. MicroRNA-30a-5p suppresses epithelial-mesenchymal transition by targeting profilin-2 in high invasive non-small cell lung cancer cell lines. Oncol Rep. 2017;37:3146–54.

    Article  CAS  Google Scholar 

  6. Tang YN, Ding WQ, Guo XJ, et al. Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis. Nat Commun. 2015;6:8230.

    Article  Google Scholar 

  7. Zhang H, Yang W, Yan J, et al. Loss of profilin 2 contributes to enhanced epithelial-mesenchymal transition and metastasis of colorectal cancer. Int J Oncol. 2018;53:1118–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kim MJ, Lee YS, Han GY, et al. Profilin 2 promotes migration, invasion, and stemness of HT29 human colorectal cancer stem cells. Biosci Biotechnol Biochem. 2015;79:1438–46.

    Article  CAS  Google Scholar 

  9. Ma CY, Zhang CP, Zhong LP, et al. Decreased expression of profilin 2 in oral squamous cell carcinoma and its clinicopathological implications. Oncol Rep. 2011;26:813–23.

    CAS  PubMed  Google Scholar 

  10. Cui XB, Zhang SM, Xu YX, et al. PFN2, a novel marker of unfavorable prognosis, is a potential therapeutic target involved in esophageal squamous cell carcinoma. J Transl Med. 2016;14:137.

    Article  Google Scholar 

  11. Liu J, Wu Y, Wang Q, et al. Bioinformatic analysis of PFN2 dysregulation and its prognostic value in head and neck squamous carcinoma. Future Oncol. 2018;14:449–59.

    Article  CAS  Google Scholar 

  12. Zhou K, Chen J, Wu J, et al. Profilin 2 promotes proliferation and metastasis of head and neck cancer cells by regulating PI3K/AKT/beta-catenin signaling pathway. Oncol Res. 2019;27:1079–88.

    Article  Google Scholar 

  13. Liu Y, Li H, Liu F, et al. Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways. EBioMedicine. 2020;51:102583.

    Article  Google Scholar 

  14. Mouneimne G, Hansen SD, Selfors LM, et al. Differential remodeling of actin cytoskeleton architecture by profilin isoforms leads to distinct effects on cell migration and invasion. Cancer Cell. 2012;22:615–30.

    Article  CAS  Google Scholar 

  15. Jiang M, Qiu N, Xia H, et al. Long noncoding RNA FOXD2AS1/miR1505p/PFN2 axis regulates breast cancer malignancy and tumorigenesis. Int J Oncol. 2019;54:1043–52.

    CAS  PubMed  Google Scholar 

  16. Yao D, Dai C, Peng S. Mechanism of the mesenchymal-epithelial transition and its relationship with metastatic tumor formation. Mol Cancer Res. 2011;9:1608–20.

    Article  CAS  Google Scholar 

  17. Massague J. TGFbeta in cancer. Cell. 2008;134:215–30.

    Article  CAS  Google Scholar 

  18. Moustakas A, Heldin CH. The regulation of TGFbeta signal transduction. Development. 2009;136:3699–714.

    Article  CAS  Google Scholar 

  19. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009;19:156–72.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are in debt to Dr. Chunjie Wang and Dr. Nick Baniak (Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Canada) for reviewing the manuscript and providing professional input.

Funding

This work was supported by the Beijing Municipal Health System Academic Leaders of High-level Health Personnel Program, P.R. China (No. 2011-2-28) and Beijing Breast Disease Prevention and Treatment Society, Cancer Prevention and Treatment Research Projects, P.R. China (No. 2015-8-8).

Author information

Author notes

  1. Senior author: Zhenwen Chen.

Authors and Affiliations

  1. Department of General Surgery, Center for Thyroid and Breast Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China

    Yuwei Ling, Jing Zhao, Ye Zhao, Kaifu Li, Zhiqiang Chen & Hua Kang

  2. School of Basic Medical Sciences, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, 100069, China

    Qi Cao, Yihan Liu, Xiaoyan Du, Xueyun Huo & Zhenwen Chen

Authors
  1. Yuwei Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qi Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yihan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ye Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kaifu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhiqiang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaoyan Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xueyun Huo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hua Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhenwen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xueyun Huo or Hua Kang.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was waived because of the nature of retrospective study, and the patient data were kept confidentially. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Publisher's Note

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

Electronic supplementary material

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ling, Y., Cao, Q., Liu, Y. et al. Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of triple negative breast cancer cells. Breast Cancer 28, 368–378 (2021). https://doi.org/10.1007/s12282-020-01169-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-020-01169-x

Keywords

Search

Navigation