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Cell Rep. 2014 May 22;7(4):1156-67. doi: 10.1016/j.celrep.2014.03.068. Epub 2014 May 1.

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

Author information

1
Department of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
2
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
3
Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810, Japan; Research Center for Cooperative Projects, Graduate School of Medicine, Hokkaido University, N15-W7, Kita-ku, Sapporo 060-8638, Japan.
4
Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810, Japan.
5
Department of Biochemistry II, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
6
Department of Biochemistry, Faculty of Medicine, Shimane University, 89-1 Izumo, Shimane 693-8501, Japan.
7
Division of Molecular Pathology, Center for Neurological Disease and Cancer, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
8
Department of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Department of Pathology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Japan.
9
Department of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Division of Molecular Pathology, Center for Neurological Disease and Cancer, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: mtakaha@med.nagoya-u.ac.jp.

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.

PMID:
24794433
DOI:
10.1016/j.celrep.2014.03.068
[Indexed for MEDLINE]
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