Abstract
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.
| Original language | English |
|---|---|
| Article number | e83629 |
| Journal | PloS one |
| Volume | 8 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 30 2013 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- General
Cite this
Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo. / Kagawa, Yoshinori; Matsumoto, Shinji; Kamioka, Yuji; Mimori, Koshi; Naito, Yoko; Ishii, Taeko; Okuzaki, Daisuke; Nishida, Naohiro; Maeda, Sakae; Naito, Atsushi; Kikuta, Junichi; Nishikawa, Keizo; Nishimura, Junichi; Haraguchi, Naotsugu; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Ishii, Hideshi; Doki, Yuichiro; Matsuda, Michiyuki; Kikuchi, Akira; Mori, Masaki; Ishii, Masaru.
In: PloS one, Vol. 8, No. 12, e83629, 30.12.2013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo
AU - Kagawa, Yoshinori
AU - Matsumoto, Shinji
AU - Kamioka, Yuji
AU - Mimori, Koshi
AU - Naito, Yoko
AU - Ishii, Taeko
AU - Okuzaki, Daisuke
AU - Nishida, Naohiro
AU - Maeda, Sakae
AU - Naito, Atsushi
AU - Kikuta, Junichi
AU - Nishikawa, Keizo
AU - Nishimura, Junichi
AU - Haraguchi, Naotsugu
AU - Takemasa, Ichiro
AU - Mizushima, Tsunekazu
AU - Ikeda, Masataka
AU - Yamamoto, Hirofumi
AU - Sekimoto, Mitsugu
AU - Ishii, Hideshi
AU - Doki, Yuichiro
AU - Matsuda, Michiyuki
AU - Kikuchi, Akira
AU - Mori, Masaki
AU - Ishii, Masaru
PY - 2013/12/30
Y1 - 2013/12/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84893709139&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893709139&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0083629
DO - 10.1371/journal.pone.0083629
M3 - Article
C2 - 24386239
AN - SCOPUS:84893709139
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 12
M1 - e83629
ER -