title: Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis.
abstract: Several reports have indicated a role for the members of the G12 family of heterotrimeric G proteins (Gα12 and Gα13) in oncogenesis and tumor cell growth. The aims of the present study were to evaluate the role of G12 signaling in cervical cancer. We demonstrated that expression of the G12 proteins was highly upregulated in cervical cancer cells. Additionally, expression of the activated forms of Gα12/Gα13 but not expression of activated Gαq induced cell invasion through the activation of the RhoA family of G proteins, but had no effect on cell proliferation in the cervical cancer cells. Inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) blocked thrombin-stimulated cell invasion, but did not inhibit cell proliferation in cervical cells, whereas the inhibition of Gαq (RGS2) had no effect. Furthermore, G12 signaling was able to activate Rho proteins, and this stimulation was inhibited by p115-RGS, and Gα12-induced invasion was blocked by an inhibitor of RhoA/B/C (C3 toxin). Pharmacological inhibition of JNK remarkably decreased G12-induced JNK activation. Both a JNK inhibitor (SP600125) and a ROCK inhibitor (Y27632) reduced G12-induced JNK and c-Jun activation, and markedly inhibited G12-induced cellular invasion. Collectively, these findings demonstrate that stimulation of G12 proteins is capable of promoting invasion through RhoA/ROCK-JNK activation.
authors.affiliation: Department of Gynaecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Gynaecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, PR China. Electronic address: jinquancuijqc@163.com.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Gynaecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, PR China.
authors.forename: Wuliang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gynaecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, PR China.
authors.forename: Kehong
authors.initials: K
authors.lastname: Deng
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C066737:RHOA protein, human; D054460:rho-Associated Kinases; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein
keywords: Cervical cancer; Gα12/13; Invasion; RhoA/ROCK-JNK