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

Kelly, Patrick; Moeller, Benjamin J.; Juneja, Juhi; Booden, Michelle A.; Der, Channing J.; Daaka, Yehia; Dewhirst, Mark W.; Fields, Timothy A.; Casey, Patrick J.

doi:10.1073/pnas.0510254103

Cited by 158 publications

(210 citation statements)

References 35 publications

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“…The contraction at the trailing edge is mediated by the small GTPase RhoA (27). Recently, it has been shown that RhoA was activated by GPCR signaling, including those elicited by U46619, through G 12 heterotrimeric G proteins during invasion of cancer cells, including PC-3 (34,35). Our study suggests that TP can regulate cell migration and cytoskeleton reorganization through inducing cell contraction via activating RhoA.…”

Section: Resultsmentioning

confidence: 50%

Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho

et al. 2008

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Thromboxane A 2 (TxA 2 ) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product prostaglandin H 2 as the substrate. Previously, increased expression of thromboxane synthase was found in prostate tumors, and tumor cell motility was attenuated by inhibitors of thromboxane synthase. This study was undertaken to elucidate how tumor motility is regulated by TxA 2 . Here, we report that human prostate cancer cells express functional receptors for TxA 2 (TP). Ligand binding assay found that PC-3 cells binded to SQ29548, a high-affinity TP antagonist, in a saturable manner with K d of 3.64 nmol/L and B max of 120.4 fmol per million cells. Treatment of PC-3 cells by U46619, a TP agonist, induced PC-3 cell contraction, which was blocked by pretreatment with the TP antagonist SQ29548 or pinane TxA 2 . The migration of prostate cancer cells was significantly inhibited either by sustained activation of TP or by blockade of TP activation, suggesting that TP activation must be tightly controlled during cell migration. Further studies found that small GTPase RhoA was activated by TP activation, and pretreatment of PC-3 cells with Y27632, a Rho kinase (ROCK) inhibitor, blocked U46619-induced cell contraction. A dominant-negative mutant of RhoA also blocked U46619-induced cell contraction. Taken together, the data suggest that TPs are expressed in prostate cancer and activation of TPs regulates prostate cancer cell motility and cytoskeleton reorganization through activation of Rho. [Cancer Res 2008;68(1):115-21]

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Section: Resultsmentioning

confidence: 50%

Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho

et al. 2008

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“…The invasion and migration assays was performed (Kelly et al, 2006a;Kelly et al, 2006b) by using a 24-well transwell chamber with 8-um pore size polycarbonate membrane (Corning, USA) as recommended by the supplier. For invasion assay, the upper side of polycarbonate filter was coated with matrigel (30 ul, diluted in 1:3, BD, Biosciences).…”

Section: Cell Invasion and Migration Assaysmentioning

confidence: 99%

Lentivirus Mediated GOLPH3 shRNA Inhibits Growth and Metastasis of Esophageal Squamous Cancer

Wang

Wang²,

Zhang³

2013

Asian Pacific Journal of Cancer Prevention

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Aim: To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer. Methods: A lentiviral shRNA-vector was utilized to stably knockdown GOLPH3 in Eca-109 esophageal squamous cancer cells. mRNA transcription and protein expression of GOLPH3 were examined by real-time quantitative PCR and Western blotting, respectively. Cell proliferation activity was assessed by MTT assay and invasion and migration potentials by matrigel invasion and transwell motility assays. Results: Stable knockdown in the GOLPH3 cell line was established. PD-A gene expression was significantly suppressed by lentivirus-mediated RNAi, which resulted in reducing the capacity for cell proliferation, migration, invasion and adhesion in vitro. In vivo, GOLPH3 depletion resulted in inhibition of tumour growth, with stable decrease in the expression of GOLPH3 in tumor xenografts. Conclusions: Our findings suggest that lentivirus mediated silencing of the GOLPH3 gene has a significant anti-tumour effect on esophageal squamous cancer in vitro and in vivo. In addition, the results indicate that GOLPH3 might be an effective molecular target for gene therapy in esophageal squamous cancer.

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“…Interaction of SW480 and CT26 with ADAM10 stimulates RhoA activity As the interaction of Ga13 with RhoA leads to an increase in cell cortical tension as well as in disruption of plasma membrane-cortical actin, 22,23 we investigated whether the interaction of SW480 and CT26 cells with ADAM10Cys-EGFP or ADAM10-EGFP activates Rho small GTPase. To this end, we performed a GTP-RhoA pull-down assay.…”

Section: Adam10 and Cd81 Regulate Localization Of Gtp-binding A13mentioning

confidence: 99%

Cell fusion promotes chemoresistance in metastatic colon carcinoma

et al. 2012

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Chemoresistance is an important concern in the treatment of metastatic colon cancer. It may emerge through selection of clones that are inherently resistant from the outset or through mechanisms acquired during treatment. Cell fusion represents an efficient means of rapid phenotypic evolution that make cells with new properties at a rate exceeding that achievable by random mutagenesis. Here, we first identified a number of proteins involved in cell fusion using a shotgun proteomics approach, then we investigated the role of these proteins namely tetraspanin CD81/CD9, ADAM10, GTP-binding protein a13, radixin, myosin regulatory light chain and RhoA in the regulation of colon cancer cell fusion. We also found a previously unrecognized role of ADAM10, Ga13 and RhoA in promoting cell fusion. Finally, we show that the occurrence of cell fusion in a metastatic model of colon carcinoma causes the appearance of cells resistant to both 5-fluorouracil and oxaliplatin. These findings highlight the importance of cell fusion in cancer progression and raise significant implications for overcoming chemoresistance in metastatic colon cancer.

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

Cited by 158 publications

References 35 publications

Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho

Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho

Lentivirus Mediated GOLPH3 shRNA Inhibits Growth and Metastasis of Esophageal Squamous Cancer

Cell fusion promotes chemoresistance in metastatic colon carcinoma

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