RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility

Yao, Huaxiong; Dashner, Erica J.; Golen, Cynthia M. van; Golen, Kenneth L. van

doi:10.1038/sj.onc.1209260

Cited by 64 publications

(78 citation statements)

References 70 publications

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“…Moreover, a number of previous reports demonstrate that increased RhoA/C activity can promote invasion of prostate (48,51,52) and other cancers (41,(53)(54)(55). Thus, it was not surprising that G 12 -induced Rho activation was strictly required for G 12 -induced prostate cancer cell invasion.…”

Section: Discussionmentioning

confidence: 95%

“…Interestingly, it appears that G␣ 12 is up-regulated at similar points in both breast (30) and prostate cancer development. In addition, it appears that this increase in G␣ 12 and G␣ 13 expression seen in prostate cancer parallels the increase in expression previously reported for the Rho GTPases (47,48) and several of the GPCRs known to promote prostate cancer cell invasion and metastasis DU145 cells were transduced with the indicated adenovirus and then starved for 18 h. Cells were lysed, and lysates were subjected to pull-down assays using a GST fusion of the activated RhoA-binding domain of rhotekin. Levels of precipitated RhoA were determined by immunoblot analysis (IB) using anti-RhoA antibody.…”

Section: Discussionmentioning

confidence: 99%

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A Role for the G12 Family of Heterotrimeric G Proteins in Prostate Cancer Invasion

Kelly

Stemmle

Madden

et al. 2006

Journal of Biological Chemistry

124

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Many studies have suggested a role for the members of the G 12 family of heterotrimeric G proteins (G␣ 12 and G␣ 13 ) in oncogenesis and tumor cell growth. However, few studies have examined G 12 signaling in actual human cancers. In this study, we examined the role of G 12 signaling in prostate cancer. We found that expression of the G 12 proteins is significantly elevated in prostate cancer. Interestingly, expression of the activated forms of G␣ 12 or G␣ 13 in the PC3 and DU145 prostate cancer cell lines did not promote cancer cell growth. Instead, expression of the activated forms of G␣ 12 or G␣ 13 in these cell lines induced cell invasion through the activation of the RhoA family of G proteins. Furthermore, inhibition of G 12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) in the PC3 and DU145 cell lines did not reduce cancer cell growth. However, inhibition of G 12 signaling with p115-RGS in these cell lines blocked thrombin-and thromboxane A2-stimulated cell invasion. These observations identify the G 12 family proteins as important regulators of prostate cancer invasion and suggest that these proteins may be targeted to limit invasion-and metastasis-induced prostate cancer patient mortality.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

A Role for the G12 Family of Heterotrimeric G Proteins in Prostate Cancer Invasion

Kelly

Stemmle

Madden

et al. 2006

Journal of Biological Chemistry

124

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“…The regulation of RhoA and RhoC activation and the mechanisms by which these GTPases influence cell functions differently are two key issues that need to be addressed. The fact that the RhoA and RhoC sequences differ significantly only in their COOH-termini (25) arguing that the opposing effects of these two isoforms on invasion resides in these COOH sequences [24] . The siRNA cells we have generated should be quite useful for assessing this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

RhoA and RhoC -siRNA inhibit the proliferation and invasiveness activity of human gastric carcinoma by Rho/PI3K/Akt pathway

Sun

Tong²,

He³

et al. 2007

WJG

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AIM:To evaluate the effects of adenovirus-mediated gene transfer of RhoA siRNA and RhoC siRNA on proliferation and invasion of SGC7901 cells by Rho/ PI3K/Akt pathway. METHODS:Plasmid of RhoA siRNA and RhoC siRNA were constructed and transfected into SGC7901 cells. siRNA and LY294002 (PI3K inhibitor) were designed as the control group. The mRNA and protein expressions of RhoA and RhoC were respectively detected with RT-PCR and western blotting. In order to find out the changes of proliferation and invasion power of SGC7901 cell lines, we analyzed the data by MTT, Boyden chamber and evaluated apoptosis of cell with flow cytometry. We treated BALB /C nude mice with RhoA and RhoC-siRNA, and tumor control rate (%) in nude mice was calculated. RESULTS:R h o A a n d R h o C s i R N A t ra n s fe c t i o n s specifically down-regulated the corresponding mRNA and protein levels in SGC7901 Cells.The experiment of permeated artificial basal membrane showed that the invasion power of SGC7901 cell lines are on the decline after treatment of Ad-RhoA and RhoC-siRNA (12.64 ± 3.27 vs 87.38 ± 17.38, P < 0.

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“…Elevated IGF-IR is found in many tumor malignancies, including breast, prostate, and lung cancers (18,19). In addition, overexpression of IGF-IR has been associated with disease progression and cancer metastasis (20,21).…”

Section: Introductionmentioning

confidence: 99%

Superior Antitumor Activity of a Novel Bispecific Antibody Cotargeting Human Epidermal Growth Factor Receptor 2 and Type I Insulin-like Growth Factor Receptor

Chen¹,

Zhang²,

Li³

et al. 2014

Molecular Cancer Therapeutics

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The humanized anti-HER2 monoclonal antibody (mAb) trastuzumab (Herceptin; Genentech) effectively inhibits human epidermal growth factor receptor 2 (HER2)-positive breast tumors. However, many patients responding to treatment often develop resistance. Cross-talk between type I insulin-like growth factor receptor (IGF-IR) and HER2 and elevated IGF-IR signaling have been implicated in tumor cell resistance to trastuzumab therapy. Previously, we reported that the anti-IGF-IR mAb m590 inhibits proliferation and migration of breast cancer MCF-7 cells in vitro. Here, we generated a "knobs-into-holes" bispecific antibody (Bi-Ab) against HER2 and IGF-IR by engineering trastuzumab and m590. We compared the effects of Bi-Ab treatment in vitro and in SKOV-3 HER2-and IGF-IR-overexpressing cancer xenograft mouse model with those of m590 and trastuzumab treatment alone or in combination. Bi-Ab effectively inhibited proliferation of HER2-and IGF-IR-overexpressing ovarian cancer SKOV-3 cells in vitro by ablating receptor phosphorylation and downstream PI3K/Akt and mitogen-activated protein kinase signaling. Bi-Ab more effectively inhibited cancer growth in SKOV-3 HER2-and IGF-IR-overexpressing cancer xenograft mouse model than m590 and trastuzumab alone or in combination. Mice bearing SKOV-3 HER2-and IGF-IR-overexpressing xenografts showed extensive and sustainable tumor regression when treated with Bi-Ab. Our results suggest that Bi-Ab has superior antitumor activity compared with monospecific antibodies, and cotargeting HER2 and IGF-IR may be clinically beneficial in minimizing the acquired resistance to trastuzumab therapy. Mol Cancer Ther; 13(1); 90-100. Ó2013 AACR.

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RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility

Cited by 64 publications

References 70 publications

A Role for the G12 Family of Heterotrimeric G Proteins in Prostate Cancer Invasion

A Role for the G12 Family of Heterotrimeric G Proteins in Prostate Cancer Invasion

RhoA and RhoC -siRNA inhibit the proliferation and invasiveness activity of human gastric carcinoma by Rho/PI3K/Akt pathway

Superior Antitumor Activity of a Novel Bispecific Antibody Cotargeting Human Epidermal Growth Factor Receptor 2 and Type I Insulin-like Growth Factor Receptor

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