Skip to main content
Log in

Protein interactions of cortactin in relation to invadopodia formation in metastatic renal clear cell carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

In the present study, we wanted to examine the predominant factor/s in the initiation of metastasis. We used samples of advanced grades of renal clear cell carcinoma with documented clinical history of vena caval spread as the experimental group. The major rationale for this selection is the fact that renal cell carcinoma metastasize extensively through the inferior vena cava up to the pulmonary bed and often exist as a continuous mass of metastatic tissue. As cortactin plays a significant role in invadopodia formation during initiation of metastasis, in the present study, we tested expression of cortactin and phosphotyr421-cortactin in different grades of renal cell clear carcinoma and examined its property to bind to actin. The findings of the present study suggest that the variations of the local physiological milieu are the driving forces for metastasis by enhancing molecular mechanisms for lamellipodia formation. We conclude that localization of cortactin in cancer cells and interaction between actin and its nucleators are crucial for cancer progression.

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

Access this article

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

References

  1. McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014;16:717–27.

    Article  CAS  PubMed  Google Scholar 

  2. Orgaz JL, Herraiz C, Sanz-Moreno V. Rho GTPases modulate malignant transformation of tumor cells. Small GTPases. 2014;5:e29019.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Scheel C, Weinberg RA. Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Semin Cancer Biol. 2012;22:396–403.

    Article  CAS  PubMed  Google Scholar 

  4. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147:275–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nantajit D, Lin D, Li JJ. The network of epithelial-mesenchymal transition: potential new targets for tumor resistance. J Cancer Res Clin Oncol. 2014.

  6. Gonzalez DM, Medici D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal. 2014;7:re8.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Derynck R, Muthusamy BP, Saeteurn KY. Signaling pathway cooperation in TGF-β-induced epithelial-mesenchymal transition. Curr Opin Cell Biol. 2014;31C:56–66.

    Article  Google Scholar 

  8. Giarnieri E, Bellipanni G, Macaluso M, Mancini R, Holstein AC, Milanese C, et al. Review: cell dynamics in malignant pleural effusions. J Cell Physiol. 2014.

  9. Moyret-Lalle C, Ruiz E, Puisieux A. Epithelial-mesenchymal transition transcription factors and miRNAs: “plastic surgeons” of breast cancer. World J Clin Oncol. 2014;5:311–22.

    Article  PubMed  PubMed Central  Google Scholar 

  10. O’Connor JW, Gomez EW. Biomechanics of TGFβ-induced epithelial-mesenchymal transition: implications for fibrosis and cancer. Clin Transl Med. 2014;3:23.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Martin TA. The role of tight junctions in cancer metastasis. Semin Cell Dev Biol. 2014.

  12. Wong TS, Gao W, Chan JY. Transcription regulation of E-cadherin by zinc finger E-box binding homeobox proteins in solid tumors. Biomed Res Int. 2014;2014:921564.

    PubMed  PubMed Central  Google Scholar 

  13. Chiodoni C, Colombo MP, Sangaletti S. Matricellular proteins: from homeostasis to inflammation, cancer, and metastasis. Cancer Metastasis Rev. 2010;29:295–307.

    Article  CAS  PubMed  Google Scholar 

  14. Wells A, Chao YL, Grahovac J, Wu Q, Lauffenburger DA. Epithelial and mesenchymal phenotypic switchings modulate cell motility in metastasis. Front Biosci (Landmark Ed). 2011;16:815–37.

    Article  CAS  Google Scholar 

  15. Conti A, Santoni M, Amantini C, Burattini L, Berardi R, Santoni G, et al. Progress of molecular targeted therapies for advanced renal cell carcinoma. Biomed Res Int. 2013;2013:419176.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Géraud C, Koch PS, Damm F, Schledzewski K, Goerdt S. The metastatic cycle: metastatic niches and cancer cell dissemination. J Dtsch Dermatol Ges. 2014.

  17. Khan MI, Czarnecka AM, Duchnowska R, Kukwa W, Szczylik C. Metastasis-initiating cells in renal cancer. Curr Signal Transduct Ther. 2014;8:240–6.

    Article  PubMed  Google Scholar 

  18. Singleton PA. Hyaluronan regulation of endothelial barrier function in cancer. Adv Cancer Res. 2014;123:191–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ouderkirk JL, Krendel M. Non-muscle myosins in tumor progression, cancer cell invasion, and metastasis. Cytoskeleton (Hoboken). 2014;71:447–63.

    Article  CAS  Google Scholar 

  20. Wang CL, Coluccio LM. New insights into the regulation of the actin cytoskeleton by tropomyosin. Int Rev Cell Mol Biol. 2010;281:91–128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chawla A, Mishra D, Bansal R, Chundru M. Rare sites of delayed metastasis in renal cell carcinoma. BMJ Case Rep. 2013;2013.

  22. Casey RG, Raheem OA, Elmusharaf E, Madhavan P, Tolan M, Lynch TH. Renal cell carcinoma with IVC and atrial thrombus: a single centre’s 10 year surgical experience. Surgeon. 2013;11:295–9.

    Article  CAS  PubMed  Google Scholar 

  23. Abel EJ, Wood CG, Eickstaedt N, Fang JE, Kenney P, Bagrodia A, et al. Preoperative pulmonary embolism does not predict poor postoperative outcomes in patients with renal cell carcinoma and venous thrombus. J Urol. 2013;190:452–7.

    Article  PubMed  Google Scholar 

  24. Narumiya S, Tanji M, Ishizaki T. Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer Metastasis Rev. 2009;28:65–76.

    Article  CAS  PubMed  Google Scholar 

  25. Weed SA, Parsons JT. Cortactin: coupling membrane dynamics to cortical actin assembly. Oncogene. 2001;20:6418–34.

    Article  CAS  PubMed  Google Scholar 

  26. Schuuring E. The involvement of the chromosome 11q13 region in human malignancies: cyclin D1 and EMS1 are two new candidate oncogenes—a review. Gene. 1995;159:83–96.

    Article  CAS  PubMed  Google Scholar 

  27. Balzer EM, Whipple RA, Thompson K, Boggs AE, Slovic J, Cho EH, et al. c-Src differentially regulates the functions of microtentacles and invadopodia. Oncogene. 2010;29:6402–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Faragalla H, Al-Haddad S, Stewart R, Yousef GM. The significance of florid giant cell component in renal cell carcinoma: a case report and review of the literature. Can J Urol. 2010;17:5219–22.

    PubMed  Google Scholar 

  29. Macdonald A, Horwitz AR, Lauffenburger DA. Kinetic model for lamellipodal actin-integrin ‘clutch’ dynamics. Cell Adhes Migr. 2008;2:95–105.

    Article  Google Scholar 

  30. Eke I, Deuse Y, Hehlgans S, Gurtner K, Krause M, Baumann M, et al. β1 integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy. J Clin Invest. 2012;122:1529–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhang K, Wang D, Song J. Cortactin is involved in transforming growth factor-beta1-induced epithelial-mesenchymal transition in AML-12 cells. Acta Biochim Biophys Sin (Shanghai). 2009;41:839–45.

    Article  CAS  Google Scholar 

  32. Boguslavsky S, Grosheva I, Landau E, Shtutman M, Cohen M, Arnold K, et al. p120 catenin regulates lamellipodial dynamics and cell adhesion in cooperation with cortactin. Proc Natl Acad Sci U S A. 2007;104:10882–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kirkbride KC, Sung BH, Sinha S, Weaver AM. Cortactin: a multifunctional regulator of cellular invasiveness. Cell Adhes Migr. 2011;5:187–98.

    Article  Google Scholar 

  34. Wang GC, Hsieh PS, Hsu HH, Sun GH, Nieh S, Yu CP, et al. Expression of cortactin and survivin in renal cell carcinoma associated with tumor aggressiveness. World J Urol. 2009;27:557–63.

    Article  CAS  PubMed  Google Scholar 

  35. Matsuo T, Miyata Y, Watanabe S, Ohba K, Hayashi T, Kanda S, et al. Pathologic significance and prognostic value of phosphorylated cortactin expression in patients with sarcomatoid renal cell carcinoma. Urology. 2011;78(2):476.e9–15.

    Article  Google Scholar 

  36. Zhang Y, Zhang M, Dong H, Yong S, Li X, Olashaw N, et al. Deacetylation of cortactin by SIRT1 promotes cell migration. Oncogene. 2009;28(3):445–60.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ye Tian.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, HL., Liu, QJ., Yang, PQ. et al. Protein interactions of cortactin in relation to invadopodia formation in metastatic renal clear cell carcinoma. Tumor Biol. 36, 3417–3422 (2015). https://doi.org/10.1007/s13277-014-2976-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2976-8

Keywords

Navigation