Open Access

UNC5C‑knockdown enhances the growth and metastasis of breast cancer cells by potentiating the integrin α6/β4 signaling pathway

  • Authors:
    • Mingjing Yuan
    • Fuan Xie
    • Xianyuan Xia
    • Kai Zhong
    • Lanlan Lian
    • Shihui Zhang
    • Li Yuan
    • Jun Ye
  • View Affiliations

  • Published online on: December 2, 2019     https://doi.org/10.3892/ijo.2019.4931
  • Pages: 139-150
  • Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Unc‑5 Netrin Receptor C (UNC5C) is a netrin‑1 dependence receptor that mediates the induction of apoptosis in the absence of netrin‑1. The present study found that UNC5C is heterogeneously expressed in breast cancer cell lines. By knocking down UNC5C in SK‑BR‑3 and ZR‑75‑30 cells and overexpressing UNC5c in MDA‑MB‑231 cells, it was demonstrated that UNC5C exerts an inhibitory effect on the growth and metastasis of breast cancer cells. The mechanism involved a UNC5C‑knockdown‑induced enhancement of matrix metalloproteinase (MMP)3, MMP7, MMP9 and MMP10 expression via activation of the PI3K/AKT, ERK and p38 MAPK signaling pathways. Notably, UNC5C directly interacted with integrin α6, which is involved in the growth and metastasis of breast cancer cells. Additionally, UNC5C‑knockdown enhanced the phosphorylation of FAK and SRC, which are key kinases in the netrin‑1/Unc5C and netrin‑1/integrin α6/β4 signaling pathways. This suggests that netrin‑1 functions as an integrator for both the netrin‑1/Unc5C and netrin‑1/integrin α6/β4 signaling pathways. UNC5C‑knockdown potentiated netrin‑1/integrin α6/β4 signaling. Given that UNC5C‑knockdown inhibited integrin‑liked protein kinase phosphorylation at Thr‑173, at least in SK‑BR‑3 cells, this may be an inhibitory phosphorylation site rather than activating phosphorylation site for relaying integrin signaling.
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January 2020
Volume 56 Issue 1

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

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APA
Yuan, M., Xie, F., Xia, X., Zhong, K., Lian, L., Zhang, S. ... Ye, J. (2020). UNC5C‑knockdown enhances the growth and metastasis of breast cancer cells by potentiating the integrin α6/β4 signaling pathway. International Journal of Oncology, 56, 139-150. https://doi.org/10.3892/ijo.2019.4931
MLA
Yuan, M., Xie, F., Xia, X., Zhong, K., Lian, L., Zhang, S., Yuan, L., Ye, J."UNC5C‑knockdown enhances the growth and metastasis of breast cancer cells by potentiating the integrin α6/β4 signaling pathway". International Journal of Oncology 56.1 (2020): 139-150.
Chicago
Yuan, M., Xie, F., Xia, X., Zhong, K., Lian, L., Zhang, S., Yuan, L., Ye, J."UNC5C‑knockdown enhances the growth and metastasis of breast cancer cells by potentiating the integrin α6/β4 signaling pathway". International Journal of Oncology 56, no. 1 (2020): 139-150. https://doi.org/10.3892/ijo.2019.4931