TY - JOUR
T1 - TRIM27/MRTF-B-dependent integrin β1 expression defines leading cells in cancer cell collectives
AU - Kato, Takuya
AU - Enomoto, Atsushi
AU - Watanabe, Takashi
AU - Haga, Hisashi
AU - Ishida, Sumire
AU - Kondo, Yuji
AU - Furukawa, Koichi
AU - Urano, Takeshi
AU - Mii, Shinji
AU - Weng, Liang
AU - Ishida-Takagishi, Maki
AU - Asai, Masato
AU - Asai, Naoya
AU - Kaibuchi, Kozo
AU - Murakumo, Yoshiki
AU - Takahashi, Masahide
N1 - Funding Information:
We gratefully acknowledge Dr. Mutsuki Amano (Nagoya University) for providing expression-vector-encoding GFP-tagged RhoE. We are grateful to Dr. Mikito Takefuji (Nagoya University) for helpful discussions. We would like to thank Kaori Ushida, Koichi Imaizumi, and Kozo Uchiyama for technical assistance. This work was supported by Grants-in-Aid for Global Center of Excellence (GCOE) Research, Scientific Research (A), Challenging Exploratory Research, Scientific Research on Innovative Areas (to M.T.) and a Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T.K.).
PY - 2014/5/22
Y1 - 2014/5/22
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2014.03.068
DO - 10.1016/j.celrep.2014.03.068
M3 - Article
C2 - 24794433
AN - SCOPUS:84901263566
SN - 2211-1247
VL - 7
SP - 1156
EP - 1167
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -
