Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.
The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell...
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Public Library of Science (PLoS)
2013
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oai:doaj.org-article:67087f6a19784b1b98c95ec16a361c2a2021-11-18T08:39:54ZCell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.1932-620310.1371/journal.pone.0083629https://doaj.org/article/67087f6a19784b1b98c95ec16a361c2a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386239/?tool=EBIhttps://doaj.org/toc/1932-6203The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.Yoshinori KagawaShinji MatsumotoYuji KamiokaKoshi MimoriYoko NaitoTaeko IshiiDaisuke OkuzakiNaohiro NishidaSakae MaedaAtsushi NaitoJunichi KikutaKeizo NishikawaJunichi NishimuraNaotsugu HaraguchiIchiro TakemasaTsunekazu MizushimaMasataka IkedaHirofumi YamamotoMitsugu SekimotoHideshi IshiiYuichiro DokiMichiyuki MatsudaAkira KikuchiMasaki MoriMasaru IshiiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83629 (2013) |
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DOAJ |
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DOAJ |
| language |
EN |
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Medicine R Science Q |
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Medicine R Science Q Yoshinori Kagawa Shinji Matsumoto Yuji Kamioka Koshi Mimori Yoko Naito Taeko Ishii Daisuke Okuzaki Naohiro Nishida Sakae Maeda Atsushi Naito Junichi Kikuta Keizo Nishikawa Junichi Nishimura Naotsugu Haraguchi Ichiro Takemasa Tsunekazu Mizushima Masataka Ikeda Hirofumi Yamamoto Mitsugu Sekimoto Hideshi Ishii Yuichiro Doki Michiyuki Matsuda Akira Kikuchi Masaki Mori Masaru Ishii Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo. |
| description |
The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers. |
| format |
article |
| author |
Yoshinori Kagawa Shinji Matsumoto Yuji Kamioka Koshi Mimori Yoko Naito Taeko Ishii Daisuke Okuzaki Naohiro Nishida Sakae Maeda Atsushi Naito Junichi Kikuta Keizo Nishikawa Junichi Nishimura Naotsugu Haraguchi Ichiro Takemasa Tsunekazu Mizushima Masataka Ikeda Hirofumi Yamamoto Mitsugu Sekimoto Hideshi Ishii Yuichiro Doki Michiyuki Matsuda Akira Kikuchi Masaki Mori Masaru Ishii |
| author_facet |
Yoshinori Kagawa Shinji Matsumoto Yuji Kamioka Koshi Mimori Yoko Naito Taeko Ishii Daisuke Okuzaki Naohiro Nishida Sakae Maeda Atsushi Naito Junichi Kikuta Keizo Nishikawa Junichi Nishimura Naotsugu Haraguchi Ichiro Takemasa Tsunekazu Mizushima Masataka Ikeda Hirofumi Yamamoto Mitsugu Sekimoto Hideshi Ishii Yuichiro Doki Michiyuki Matsuda Akira Kikuchi Masaki Mori Masaru Ishii |
| author_sort |
Yoshinori Kagawa |
| title |
Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo. |
| title_short |
Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo. |
| title_full |
Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo. |
| title_fullStr |
Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo. |
| title_full_unstemmed |
Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo. |
| title_sort |
cell cycle-dependent rho gtpase activity dynamically regulates cancer cell motility and invasion in vivo. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/67087f6a19784b1b98c95ec16a361c2a |
| work_keys_str_mv |
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