TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives
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 int...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-05-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714002782 |
| _version_ | 1819050341330583552 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Takuya Kato |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T11:46:30Z |
| format | Article |
| id | doaj.art-493e936aeb0c4adf82153c7944217034 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T11:46:30Z |
| publishDate | 2014-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-493e936aeb0c4adf82153c79442170342022-12-21T19:05:09ZengElsevierCell Reports2211-12472014-05-01741156116710.1016/j.celrep.2014.03.068TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell CollectivesTakuya Kato0Atsushi Enomoto1Takashi Watanabe2Hisashi Haga3Sumire Ishida4Yuji Kondo5Koichi Furukawa6Takeshi Urano7Shinji Mii8Liang Weng9Maki Ishida-Takagishi10Masato Asai11Naoya Asai12Kozo Kaibuchi13Yoshiki Murakumo14Masahide Takahashi15Department of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanTransdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810, JapanTransdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810, JapanDepartment of Biochemistry II, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Biochemistry II, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Biochemistry, Faculty of Medicine, Shimane University, 89-1 Izumo, Shimane 693-8501, JapanDepartment of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDivision of Molecular Pathology, Center for Neurological Disease and Cancer, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Pathology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanFor 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.http://www.sciencedirect.com/science/article/pii/S2211124714002782 |
| spellingShingle | 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 TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives Cell Reports |
| title | TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives |
| title_full | TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives |
| title_fullStr | TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives |
| title_full_unstemmed | TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives |
| title_short | TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives |
| title_sort | trim27 mrtf b dependent integrin β1 expression defines leading cells in cancer cell collectives |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714002782 |
| work_keys_str_mv | AT takuyakato trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT atsushienomoto trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT takashiwatanabe trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT hisashihaga trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT sumireishida trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT yujikondo trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT koichifurukawa trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT takeshiurano trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT shinjimii trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT liangweng trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT makiishidatakagishi trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT masatoasai trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT naoyaasai trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT kozokaibuchi trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT yoshikimurakumo trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives AT masahidetakahashi trim27mrtfbdependentintegrinb1expressiondefinesleadingcellsincancercellcollectives |