title: Formin-like2 regulates Rho/ROCK pathway to promote actin assembly and cell invasion of colorectal cancer.
abstract: Formin-like2 (FMNL2) is a member of the diaphanous-related formins family, which act as effectors and upstream modulators of Rho GTPases signaling and control the actin-dependent processes, such as cell motility or invasion. FMNL2 has been identified as promoting the motility and metastasis in colorectal carcinoma (CRC). However, whether FMNL2 regulates Rho signaling to promote cancer cell invasion remains unclear. In this study, we demonstrated an essential role for FMNL2 in the activations of Rho/ROCK pathway, SRF transcription or actin assembly, and subsequent CRC cell invasion. FMNL2 could activate Rho/ROCK pathway, and required ROCK to promote CRC cell invasion. Moreover, FMNL2 promoted the formation of filopodia and stress fiber, and activated the SRF transcription in a Rho-dependent manner. We also demonstrated that FMNL2 was necessary for LPA-induced invasion, RhoA/ROCK activation, actin assembly and SRF activation. FMNL2 was an essential component of LPA signal transduction toward RhoA by directly interacting with LARG. LARG silence inhibited RhoA/ROCK pathway and CRC cell invasion. Collectively, these data indicate that FMNL2, acting as upstream of RhoA by interacting with LARG, can promote actin assembly and CRC cell invasion through a Rho/ROCK-dependent mechanism.
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Department of Pathology, the People's Hospital, Nanchang, China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Yudan
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Department of Oncology, General Hospital of Armed Police Forces, Beijing, China.
authors.forename: Xiling
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Guoyang
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000199:Actins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000473:pathology*; D004789:Enzyme Activation; D000080865:Formins; D019073:HT29 Cells; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011506:Proteins / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: C577222:ARHGEF12 protein, human; D000199:Actins; C476208:FMNL2 protein, human; D000080865:Formins; D008246:Lysophospholipids; D011506:Proteins; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors; D026362:Serum Response Factor; D054460:rho-Associated Kinases; C066690:RHOC protein, human; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein; C032881:lysophosphatidic acid
keywords: Colorectal cancer; FMNL2; LARG; Rho/ROCK signaling; invasion