Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization

Xiaoze Wang, Atsushi Enomoto, Liang Weng, Yasuyuki Mizutani, Shaniya Abudureyimu, Nobutoshi Esaki, Yuta Tsuyuki, Chen Chen, Shinji Mii, Naoya Asai, Hisashi Haga, Sumire Ishida, Kenji Yokota, Masashi Akiyama, Masahide Takahashi

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5 Citations (Scopus)

Abstract

Pathological observations show that cancer cells frequently invade the surrounding stroma in collective groups rather than through single cell migration. Here, we studied the role of the actin-binding protein Girdin, a specific regulator of collective migration of neuroblasts in the brain, in collective cancer cell migration. We found that Girdin was essential for the collective migration of the skin cancer cell line A431 on collagen gels as well as their fibroblast-led collective invasion in an organotypic culture model. We provide evidence that Girdin binds to β-catenin that plays important roles in the Wnt signaling pathway and in E-cadherin-mediated cell-cell adhesion. Girdin-depleted cells displayed scattering and impaired E-cadherin-specific cell-cell adhesion. Importantly, Girdin depletion led to impaired cytoskeletal association of the β-catenin complex, which was accompanied by changes in the supracellular actin cytoskeletal organization of cancer cell cohorts on collagen gels. Although the underlying mechanism is unclear, this observation is consistent with the established role of the actin cytoskeletal system and cell-cell adhesion in the collective behavior of cells. Finally, we showed the correlation of the expression of Girdin with that of the components of the E-cadherin complex and the differentiation of human skin cancer. Collectively, our results suggest that Girdin is an important modulator of the collective behavior of cancer cells.

Original languageEnglish
Pages (from-to)3643-3656
Number of pages14
JournalCancer science
Volume109
Issue number11
DOIs
Publication statusPublished - 11-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Wang, X., Enomoto, A., Weng, L., Mizutani, Y., Abudureyimu, S., Esaki, N., Tsuyuki, Y., Chen, C., Mii, S., Asai, N., Haga, H., Ishida, S., Yokota, K., Akiyama, M., & Takahashi, M. (2018). Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization. Cancer science, 109(11), 3643-3656. https://doi.org/10.1111/cas.13795