Expression and significance of RhoC gene in hepatocellular carcinoma

Wang, Wei

doi:10.3748/wjg.v9.i9.1950

Cited by 61 publications

(53 citation statements)

References 30 publications

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“…Increasing evidence from several laboratories suggests that RhoC expression is associated with particularly aggressive, metastatic cancers; however, this has never been reported for CaP (Moscow et al, 1994;del Peso et al, 1997;Fritz et al, 1999;Imamura et al, 1999;Clark et al, 2000;Sahai and Marshall, 2002;Carr et al, 2003;Horiuchi et al, 2003;Kamai et al, 2003;Marionnet et al, 2003;Shinto et al, 2003;Wang et al, 2003;Kondo et al, 2004). We hypothesized that RhoC may be involved in CaP metastasis.…”

Section: Rho Gtpase Expression In Cap Cellsmentioning

confidence: 91%

“…Although these studies demonstrate a role for these GTPases in CaP cell cytoskeletal reorganization, they have not fully made the connection with motility, invasion or metastasis. Further, it is becoming increasingly evident that the vast majority of human tumors overexpress RhoA, but overexpression of RhoC is limited to particularly aggressive and metastatic forms of cancer (Moscow et al, 1994;del Peso et al, 1997;Fritz et al, 1999;Imamura et al, 1999;Clark et al, 2000;Sahai and Marshall, 2002;Carr et al, 2003;Horiuchi et al, 2003;Kamai et al, 2003;Marionnet et al, 2003;Shinto et al, 2003;Wang et al, 2003;Kondo et al, 2004) The PC-3 cells, derived from a bone metastasis, were the only CaP cell line to express active RhoC protein.…”

Section: )mentioning

confidence: 99%

“…RhoC GTPase is a Rho protein implicated in the progression and metastasis of several cancers, including breast, ovarian, pancreas, gastric cancer, hepatocellular carcinoma, bladder, colorectal and cutaneous melanoma (Moscow et al, 1994;del Peso et al, 1997;Suwa et al, 1998;Fritz et al, 1999;van Golen et al, 1999van Golen et al, , 2000Imamura et al, 1999;Clark et al, 2000;Sahai and Marshall 2002;Carr et al, 2003;Horiuchi et al, 2003;Kamai et al, 2003;Marionnet et al, 2003;Shinto et al, 2003;Wang et al, 2003;Kondo et al, 2004). Our laboratory has demonstrated that ectopic expression of wild-type RhoC in immortalized human mammary epithelial cells leads to a metastatic phenotype (van Golen et al, 2000a, b).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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Section: Rho Gtpase Expression In Cap Cellsmentioning

confidence: 91%

Section: )mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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“…The three putative candidate sequences and one control sequences were as follows: sequence 1 sense 5 ¶-GATCCCCGACCTGCCTCCTCATCGTCTTCAAGAGAGACGATGAG-GAGGCAGGTCTTTTTA-3 ¶ and antisense 5 ¶-AGCTTAAAAAGACCTGCC-TCCTCATCGTCTCTCTTGAAGACGATGAGGAGGCAGGTCGGG-3 ¶, sequence 2 sense 5 ¶-GATCCCCCATGTGCTTCTCCATCGACTTCAAGA-GAGTCGATGGAGAAGCACATGTTTTTA-3 ¶ and antisense 5 ¶-AGCT-TAAAAACATGTGCTTCTCCATCGACTCTCTTGAAGTCGATGGAGAAG-CACATGGGG-3 ¶, sequence 3 sense 5 ¶-GATCCCCTAAGAAGGACCTGA-GGCAATTCAAGAGATTGCCTCAGGTCCTTCTTATTTTTA-3 ¶ and antisense 5 ¶-AGCTTAAAAATAAGAAGGACCTGAGGCAATCTCTT-GAATTGCCTCAGGTCCTTCTTAGGG-3 ¶, and sequence control sense 5 ¶-GATCCCCCAGTCAGGAGGATCCAAAGTTCAAGAGACTTTG-GATCCTCCTGACTGTTTTTA-3 ¶ and antisense 5 ¶-AGCTTAAAAACAGTC-AGGAGGATCCAAAGTCTCTTGAACTTTGGATCCTCCTGACTGGGG-3 ¶. RNA isolation and reverse transcription-PCR. The details of real-time quantitative reverse transcription-PCR have been described previous (14). The primer sequences were as follows: RhoA, 116 bp, sense Western blotting and Rho activity assays.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Invasion and Metastasis of Hepatocellular Carcinoma Cells via Targeting RhoC In vitro and In vivo

Wang

Wu²,

Fěng³

et al. 2008

Clinical Cancer Research

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Purpose: Hepatocellular carcinoma (HCC) is one of the most deadly human cancers because of its high incidence of metastasis. Our previous work identified a strong correlation between increased expression of RhoC and HCC metastasis. Here, we investigate to define the role of RhoC in HCC metastasis. Furthermore, we sought to determine whether inhibition of the expression of RhoC might block the metastasis of HCC in vivo. Experimental Design: A stable retroviral small interfering RNA approach was employed to selectively knockdown the expression of RhoC in vitro and in vivo. Invasion and migration assay, MTT and fluorescence-activated cell sorting analysis, Rho activity assay, and immunofluorescence staining were carried out to characterize RhoC in vitro. An anti-RhoC retroviral gene delivery BALB/c nude mice model was established to investigate whether knockdown of the expression of RhoC might inhibit the metastasis of HCC in vivo. Results: We confirmed the correlation of RhoC expression and metastatic potentials of HCC cell lines.We also showed that suppression of RhoC expression resulted in inhibition of invasion and migration without an apparent effect on cell survival and proliferation in HCCLM3 cells. Furthermore, a similar effect of RhoC on autotaxin-induced invasion of HCCLM3 cells was also observed. Significantly, we successfully adopted an HCC metastatic mouse model that allowed us to show that knockdown of the RhoC expression resulted in inhibition of metastasis of HCC in vivo for the first time. Conclusions: Our results show a critical role of RhoC in metastasis of HCC, implicating RhoC as a potential therapeutic target to block HCC metastasis.Hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia and Africa, especially in China (1, 2). During the past decade, the long-term survival remains unsatisfactory because of a high incidence of recurrence and metastasis after the hepatic resection, with a 5-year actuarial recurrence rate of 75% to 100% reported in the literature (3). Thus, the inhibition of invasion and metastasis is of great importance in the HCC therapies.Available information indicates that invasion and metastasis is to a large extent attributable to the ability of cell migration (4, 5). Rho-GTPases, members of Ras superfamily of small GTPases, shuttle between inactive GDP-bound and active GTPbound form and exhibit intrinsic GTPase activities. Activation of the Rho protein leads to the assembly of the actin-myosin contractile filaments into focal adhesion complexes that lead to cell polarity and facilitate motility (6). Recently, RhoC has attracted interest because its increased expression has been linked to increased invasion in breast, melanoma, pancreatic, colon, bladder, hepatocellular, non-small cell lung carcinoma, and primary gastric tumor or cell lines (7 -13). Our previous study revealed that RhoC was a prognostic marker with HCC and its expression was correlated with invasion and metastasis of HCC (14 -16). Interestingly, a recent study using RhoCdefic...

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“…Although Rho GTPases have been implicated in human cancer (2), mutation does not appear to be a mode of Rho activation, in contrast to Ras proteins (mutated versions of Ras proteins have been detected in tumors). However, RhoA and RhoC protein levels are significantly elevated in a variety of tumors, especially during progression to more invasive and metastatic forms (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Moreover, microarray analysis of metastasis-inducing genes identified RhoC in an experimental mouse melanoma model (13).…”

Section: Introductionmentioning

confidence: 99%