RhoC-GTPase is a Novel Tissue Biomarker Associated with Biologically Aggressive Carcinomas of the Breast

Kleer, Celina G.; Griffith, Kent A.; Sabel, Michael S.; Gallagher, Gary W.; Golen, Kenneth L. van; Wu, Zhi Fen; Merajver, Sofía D.

doi:10.1007/s10549-005-4170-6

Cited by 101 publications

(92 citation statements)

References 31 publications

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“…This finding is consistent with a previous report suggesting that G␣12 and G␣13 expression is elevated in cell lines derived from metastatic human breast, prostate, and colon cancers (33). This up-regulation of G␣12 in intraepithelial neoplasms also is similar to what was previously reported for receptors that couple to the G12 protein (16,34) and the increased expression of the Rho proteins observed at this point or later in cancer development (16,35). Thus, it appears that the G12 signaling pathway is up-regulated as an invasion-promoting signaling unit as breast cancer progresses to an invasive phenotype.…”

Section: Discussionsupporting

confidence: 93%

The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis

Kelly

Moeller²,

Juneja

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

158

191

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Although the prognosis for patients with early-stage breast cancer has improved, the therapeutic options for patients with locally advanced and metastatic disease are limited. To improve the treatment of these patients, the molecular mechanisms underlying breast cancer invasion and metastasis must be understood. In this study, we report that signaling through the G12 family of heterotrimeric G proteins (G␣12 and G␣13) promotes breast cancer cell invasion. Moreover, we demonstrate that inhibition of G12 signaling reduces the metastatic dissemination of breast cancer cells in vivo. Finally, we demonstrate that the expression of G␣12 is significantly up-regulated in the earliest stages of breast cancer, implying that amplification of G12 signaling may be an early event in breast cancer progression. Taken together, these observations identify the G12 family proteins as important regulators of breast cancer invasion and suggest that these proteins may be targeted to limit invasion-and metastasis-induced patient morbidity and mortality.cadherin ͉ Rho ͉ G protein-coupled receptor

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Section: Discussionsupporting

confidence: 93%

The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis

Kelly

Moeller²,

Juneja

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

158

191

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“…1 and Ref. 11) express relatively high levels of RHOC (24,25) indicating that RHOC can be expressed in breast carcinoma cells in the absence of miR-10b. Clearly, miR-10b has significant effects on cellular functions that underlie the progression of breast and other cancers including RhoGTPase regulation, migration, and invasion.…”

Section: Discussionmentioning

confidence: 99%

miR-10b Targets Tiam1

Moriarty

Pursell

Mercurio

2010

Journal of Biological Chemistry

102

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Understanding the mechanisms by which specific microRNAs regulate cell migration and invasion is a timely and significant problem in cancer cell biology. miR-10b is of interest in this regard because its expression is altered in breast and other cancers. Our analysis of potential miR-10b targets identified Tiam1 (T lymphoma invasion and metastasis 1), a guanidine exchange factor for Rac. We demonstrate, using an miR-10b synthetic precursor, expression vector, and antisense oligonucleotide, that miR-10b represses Tiam1 expression in breast carcinoma cells and that it interacts with the 3-UTR of Tiam1. Consistent with the involvement of Tiam1 in cell motility, we observed that miR-10b suppresses the ability of breast carcinoma cells to migrate and invade. Importantly, we demonstrate that miR-10b also inhibits Tiam1-mediated Rac activation. These data provide a mechanism for the regulation of Tiam1-mediated Rac activation in breast cancer cells and need to be considered in the context of other reported functions for miR-10b. MicroRNAs (miRNAs)2 are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translational repression or mRNA degradation (1). Convincing evidence exists that miRNAs are aberrantly expressed in human cancer (2-5) and that they can affect key cell biological processes that affect tumor progression including migration, invasion, epithelial-to-mesenchymal transition (6, 7), and metastasis (8 -10). The challenge ahead is to elucidate specific mechanisms by which miRNAs regulate such processes.miR-10b expression has been reported to be significantly deregulated in breast cancer (3), and recent studies indicate that it can promote the metastasis of breast carcinoma cells (11). Given the potential importance of miR-10b in breast and other cancers, a key issue is the identification of miR-10b targets that execute its biological functions. HoxD10 has been identified as a miR-10b target, a finding that is significant because HoxD10 represses expression of the prometastatic gene RHOC (11). Most likely, however, miR-10b targets additional genes that affect the behavior of breast carcinoma cells. In the current study, we sought to identify such novel targets of miR-10b and to assess their regulation by miR-10b in the context of breast cancer cell biology. EXPERIMENTAL PROCEDURESCell Lines-The SUM159PT and SUM149PT cell lines were obtained from Dr. Steve Ethier (University of Michigan). T-47D and MDA-MB-435 cells were obtained from ATCC (Rockville, MD).RNA Isolation and miRNA Detection-Quantitative realtime PCR (qPCR) detection of the mature form of miRNAs was performed using TaqMan miRNA reverse transcription kit and TaqMan human microarray assays for miR-10b and the miR10b mutant (Ambion). U6 small nuclear RNA was used as an internal control.Oligonucleotide Transfection-Pre-miR miRNA precursor molecules (Dharmacon) are synthetic miRNA mimics designed for functional analyses and target site validation. Cells were transfected with 20 nM pre-miR hsa-miR-10b pre...

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“…The oncogenic function of the RhoC protein has been elucidated in IBC and RhoC is consistently associated with different types of advanced cancer [17,[27][28][29][30][31][32]. Comparative microarray analysis of overexpressed-RhoC and wild-type RhoC cell lines showed that RhoC overexpression can affect the expression of more than one hundred genes that are known to be involved in various biological functions such as enhancing cell cycle progression, angiogenesis, lymphangiogenesis, and cell adhesion and invasion [33].…”

Section: Discussionmentioning

confidence: 99%

Molecular epidemiologic features of inflammatory breast cancer: a comparison between Egyptian and US patients

Kleer

Banerjee

et al. 2007

Breast Cancer Res Treat

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RhoC-GTPase is a Novel Tissue Biomarker Associated with Biologically Aggressive Carcinomas of the Breast

Cited by 101 publications

References 31 publications

The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis

The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis

miR-10b Targets Tiam1

Molecular epidemiologic features of inflammatory breast cancer: a comparison between Egyptian and US patients

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