TRIM27/MRTF-B-dependent integrin β1 expression defines leading cells in cancer cell collectives

Takuya Kato, Atsushi Enomoto, Takashi Watanabe, Hisashi Haga, Sumire Ishida, Yuji Kondo, Koichi Furukawa, Takeshi Urano, Shinji Mii, Liang Weng, Maki Ishida-Takagishi, Masato Asai, Naoya Asai, Kozo Kaibuchi, Yoshiki Murakumo, Masahide Takahashi

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

For collective invasion, cancer cells form cohesive groups comprised of leading cells (LCs) at the forefront and following cells (FCs) at the rear. However, the molecular mechanisms that define LCs and FCs remain elusive. Here, we demonstrated that LCs, but not FCs, upregulated the expression of integrin β1 after the loss of intercellular adhesion. The LC-specific expression of integrin β1 was posttranscriptionally regulated by the TRIM27/MRTF-B complex in response to the loss of intercellular adhesion, thereby regulating the stability and translation of integrin β1 mRNA via microRNA-124 in LCs. Accordingly, depletion of TRIM27 and MRTF-B abrogated the upregulation of integrin β1 in LCs and blocked the invasion of cancer cell groups in vitro and in vivo. Therefore, our findings revealed that the specific function of LCs was defined by intrinsic mechanisms related to the presence of the cell's free surface, providing insights into the regulation of intratumor heterogeneity.

Original languageEnglish
Pages (from-to)1156-1167
Number of pages12
JournalCell Reports
Volume7
Issue number4
DOIs
Publication statusPublished - 22-05-2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kato, T., Enomoto, A., Watanabe, T., Haga, H., Ishida, S., Kondo, Y., Furukawa, K., Urano, T., Mii, S., Weng, L., Ishida-Takagishi, M., Asai, M., Asai, N., Kaibuchi, K., Murakumo, Y., & Takahashi, M. (2014). TRIM27/MRTF-B-dependent integrin β1 expression defines leading cells in cancer cell collectives. Cell Reports, 7(4), 1156-1167. https://doi.org/10.1016/j.celrep.2014.03.068