Open Access

Talin2 regulates invasion of human breast cancer MDA‑MB‑231 cells via alteration of the tumor microenvironment

  • Authors:
    • Zhengwei Wen
    • Yingfan Liang
    • Shengming Deng
    • Lilin Zou
    • Xiaofan Xie
    • Jifeng Yang
    • Yiwei Wu
  • View Affiliations

  • Published online on: March 21, 2019     https://doi.org/10.3892/ol.2019.10175
  • Pages: 4835-4842
  • Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The talin proteins are a key component of the extracellular matrix‑integrin‑cytoskeleton system, and our previous study suggested that talin2 contributes to the tumor invasion and metastasis processes regulated by the tumor microenvironment. In the present study, the specific effects of talin2 on the invasive ability of breast cancer cells, as well as the underlying mechanism, were investigated by creating two MDA‑MB‑231 cell lines with stable talin2 knockdown by specific RNA interference. Initially, it was confirmed that the expression levels of talin2 in human breast cancer tissues were upregulated compared with in normal adjacent tissues. Subsequently, invasion and wound healing assays revealed that depletion of talin2 in MDA‑MB‑231 cells decreased their migratory and invasive abilities. Western blot analysis demonstrated that knockdown of talin2 in MDA‑MB‑231 cells caused marked downregulation of the tumor microenvironment markers hypoxia‑inducible factor 1α, phosphorylated ribosomal protein S6 kinase, phosphorylated protein kinase B and phosphorylated mechanistic target of rapamycin. Furthermore, knockdown of talin2 decreased the basal contents of glucose and lactic acid in the breast cancer cell line. In conclusion, the findings of the present study demonstrated that talin2 knockdown may inhibit the invasive ability of human breast cancer MDA‑MB‑23l cells via alterations in the tumor microenvironment.

References

1 

American Cancer Society, . Global Cancer Facts & Figures (4th Edition). American Cancer Society. Atlanta, GA: 2018.

2 

American Cancer Society, . Breast Cancer Facts & Figures 2017–2018. American Cancer Society. Atlanta, GA: 2017.

3 

Kenny PA, Lee GY, Myers CA, Neve RM, Semeiks JR, Spellman PT, Lorenz K, Lee EH, Barcellos-Hoff MH, Petersen OW, et al: The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol Oncol. 1:84–96. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Sung SY, Hsieh CL, Wu D, Chung LW and Johnstone PA: Tumor microenvironment promotes cancer progression, metastasis and therapeutic resistance. Curr Probl Cancer. 31:36–100. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Gao Y, Liu S, Huang J, Guo W, Chen J, Zhang L, Zhao B, Peng J, Wang A, Wang Y, et al: The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. Biomed Res Int. 2014:6484592014. View Article : Google Scholar : PubMed/NCBI

6 

Debrand E, El Jai Y, Spence L, Bate N, Praekelt U, Pritchard CA, Monkley SJ and Critchley DR: Talin 2 is a large and complex gene encoding multiple transcripts and protein isoforms. FEBS J. 276:1610–1628. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Senetar MA, Moncman CL and McCann RO: Talin2 is induced during striated muscle differentiation and is targeted to stable adhesion complexes in mature muscle. Cell Motil Cytoskeleton. 64:157–173. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Tsujioka M, Yoshida K and Inouye K: Talin B is required for force transmission in morphogenesis of Dictyostelium. EMBO J. 23:2216–2225. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Huang C, Rajfur Z, Yousefi N, Chen Z, Jacobson K and Ginsberg MH: Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration. Nat Cell Biol. 11:624–630. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Jin JK, Tien PC, Cheng CJ, Song JH, Huang C, Lin SH and Gallick GE: Talin1 phosphorylation activates β1 integrins: A novel mechanism to promote prostate cancer bone metastasis. Oncogene. 34:1811–1821. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Sakamoto S, McCann RO, Dhir R and Kyprianou N: Talin1 promotes tumor invasion and metastasis via focal adhesion signaling and anoikis resistance. Cancer Res. 70:1885–1895. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Fang KP, Dai W, Ren YH, Xu YC, Zhang SM and Qian YB: Both Talin-1 and Talin-2 correlate with malignancy potential of the human hepatocellular carcinoma MHCC-97 L cell. BMC Cancer. 16:452016. View Article : Google Scholar : PubMed/NCBI

13 

Liang Y, Chen H, Ji L, Du J, Xie X, Li X and Lou Y: Talin2 regulates breast cancer cell migration and invasion by apoptosis. Oncol Lett. 16:285–293. 2018.PubMed/NCBI

14 

Sobin LH, Gospodarowicz MK and Wittekind C: TNM classification of malignant tumours (7th edition). John Wiley and Sons. 2009.

15 

World Health Organization, . Tumours of the Breast and Female Genital Organs. Oxford University Press. 2003.

16 

Liu B, Pang B, Hou X, Fan H, Liang N, Zheng S, Feng B, Liu W, Guo H, Xu S and Pang Q: Expression of high-mobility group AT-hook protein 2 and its prognostic significance in malignant gliomas. Hum Pathol. 45:1752–1758. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Wu Z, Li X, Sunkara M, Spearman H, Morris AJ and Huang C: PIPKIγ regulates focal adhesion dynamics and colon cancer cell invasion. PLoS One. 6:e247752011. View Article : Google Scholar : PubMed/NCBI

19 

Spano D and Zollo M: Tumor microenvironment: A main actor in the metastasis process. Clin Exp Metastasis. 29:381–395. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Swartz MA, Iida N, Roberts EW, Sangaletti S, Wong MH, Yull FE, Coussens LM and DeClerck YA: Tumor microenvironment complexity: Emerging roles in cancer therapy. Cancer Res. 72:2473–2480. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI

22 

Fais S, Venturi G and Gatenby B: Microenvironmental acidosis in carcinogenesis and metastases: New strategies in prevention and therapy. Cancer Metastasis Rev. 33:1095–1108. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Upadhyay M, Samal J, Kandpal M, Singh OV and Vivekanandan P: The Warburg effect: Insights from the past decade. Pharmacol Ther. 137:318–330. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Nozawa-Suzuki N, Nagasawa H, Ohnishi K and Morishige K: The inhibitory effect of hypoxic cytotoxin on the expansion of cancer stem cells in ovarian cancer. Biochem Biophys Res Commun. 457:706–711. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Macheda ML, Rogers S and Best JD: Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol. 202:654–662. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Icard P and Lincet H: A global view of the biochemical pathways involved in the regulation of the metabolism of cancer cells. Biochim Biophys Acta. 1826:423–433. 2012.PubMed/NCBI

27 

Gaikwad SM and Ray P: Non-invasive imaging of PI3K/Akt/mTOR signalling in cancer. Am J Nucl Med Mol Imaging. 2:418–431. 2012.PubMed/NCBI

28 

Edinger AL and Thompson CB: Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell. 13:2276–2288. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Polivka J Jr and Janku F: Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther. 142:164–175. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Coddou C, Sandoval R, Castro P, Lazcano P, Hevia MJ, Rokic M, Hall B, Terse A, Gonzalez-Billault C, Kulkarni AB, et al: Cyclin-dependent kinase 5 modulates the P2X2a receptor channel gating through phosphorylation of C-terminal threonine 372. Pain. 158:2155–2168. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Hixon ML, Paccagnella L, Millham R, Perez-Olle R and Gualberto A: Development of inhibitors of the IGF-IR/PI3K/Akt/mTOR pathway. Rev Recent Clin Trials. 5:189–208. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2019
Volume 17 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wen, Z., Liang, Y., Deng, S., Zou, L., Xie, X., Yang, J., & Wu, Y. (2019). Talin2 regulates invasion of human breast cancer MDA‑MB‑231 cells via alteration of the tumor microenvironment. Oncology Letters, 17, 4835-4842. https://doi.org/10.3892/ol.2019.10175
MLA
Wen, Z., Liang, Y., Deng, S., Zou, L., Xie, X., Yang, J., Wu, Y."Talin2 regulates invasion of human breast cancer MDA‑MB‑231 cells via alteration of the tumor microenvironment". Oncology Letters 17.6 (2019): 4835-4842.
Chicago
Wen, Z., Liang, Y., Deng, S., Zou, L., Xie, X., Yang, J., Wu, Y."Talin2 regulates invasion of human breast cancer MDA‑MB‑231 cells via alteration of the tumor microenvironment". Oncology Letters 17, no. 6 (2019): 4835-4842. https://doi.org/10.3892/ol.2019.10175