Open AccessGirdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization
Author(s) -
Wang Xiaoze,
Enomoto Atsushi,
Weng Liang,
Mizutani Yasuyuki,
Abudureyimu Shaniya,
Esaki Nobutoshi,
Tsuyuki Yuta,
Chen Chen,
Mii Shinji,
Asai Naoya,
Haga Hisashi,
Ishida Sumire,
Yokota Kenji,
Akiyama Masashi,
Takahashi Masahide
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13795
Subject(s) - cytoskeleton , cell adhesion , microbiology and biotechnology , cell migration , cell , adhesion , cancer cell , cancer , biology , cancer research , chemistry , genetics , organic chemistry
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.