Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and proliferation

  • Authors:
    • Lihua Qiu
    • Changlin Zhou
    • Yun Sun
    • Wen Di
    • Erica Scheffler
    • Sarah Healey
    • Nicola Kouttab
    • Wenming Chu
    • Yinsheng Wan
  • View Affiliations

  • Published online on: October 1, 2006     https://doi.org/10.3892/ijo.29.4.1003
  • Pages: 1003-1011
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Abstract

Ovarian cancer remains the leading cause of fatality among all gynecologic cancers, although promising therapies are in the making. It has been speculated that metastasis is critical for ovarian cancer, and yet the molecular mechanisms of metastasis in ovarian cancer are poorly understood. Growth factors have been proven to play important roles in cell migration associated with metastasis, and inhibition of growth factor receptors and their distinct cell signaling pathways has been intensively studied, and yet the uncovered interaction or crosstalk among various growth factor receptors complicates this otherwise promising approach. We investigated the crosstalk between EGFR and TrkB, both of which have been known to be important in cell survival and migration in response to EGF and BDNF. Our results showed that both EGF and BDNF induced cell migration and cell proliferation in cultured human ovarian cancer cells (Caov3 cell line). EGF and BDNF transactivated TrkB and EGFR respectively, and activated downstream cell survival components such as Akt. EGFR and TrkB kinase inhibitors inhibited EGF- and BDNF-induced TrkB and EGFR activation and Akt phosphorylation, and cell proliferation and migration. Using EGFR knockout cells, we further demonstrated that EGFR is required for EGF-induced cell migration. Collectively, our data indicate that EGFR and TrkB crosstalk each other in response to EGF and BDNF, leading to cell survival pathway activation in ovarian cancer cells. Our data suggest that a combination of inhibitors of both receptors with cell survival pathway inhibitors would provide a better outcome in the clinical treatment of ovarian cancer.

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October 2006
Volume 29 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Qiu, L., Zhou, C., Sun, Y., Di, W., Scheffler, E., Healey, S. ... Wan, Y. (2006). Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and proliferation. International Journal of Oncology, 29, 1003-1011. https://doi.org/10.3892/ijo.29.4.1003
MLA
Qiu, L., Zhou, C., Sun, Y., Di, W., Scheffler, E., Healey, S., Kouttab, N., Chu, W., Wan, Y."Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and proliferation". International Journal of Oncology 29.4 (2006): 1003-1011.
Chicago
Qiu, L., Zhou, C., Sun, Y., Di, W., Scheffler, E., Healey, S., Kouttab, N., Chu, W., Wan, Y."Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and proliferation". International Journal of Oncology 29, no. 4 (2006): 1003-1011. https://doi.org/10.3892/ijo.29.4.1003