title: FMNL2 is a positive regulator of cell motility and metastasis in colorectal carcinoma.
abstract: FMNL2 is a member of diaphanous-related formins which act as effectors of Rho family GTPases and control the actin-dependent processes such as cell motility or invasion. We previously found that FMNL2 overexpression in metastatic cell lines and tissues of colorectal carcinoma is associated with more aggressive tumour behaviour. Here we used gain-of-function and loss-of-function approaches to investigate the effects of FMNL2 on colorectal carcinoma in vitro and in vivo. Forced expression of FMNL2 caused a significant increase in tumour cell proliferation, motility, invasion in vitro, and metastasis in vivo, whereas FMNL2 depletion showed opposite effects. We examined gene expression profiles following knockdown of FMNL2 in SW480/M5 cells. Expression of 323 genes was up-regulated by more than two-fold, whereas 222 genes were down-regulated by more than two-fold in FMNL2-depleting SW480/M5 cells. Gene ontology analysis showed that most of genes belong to functional categories such as cell cycle, cytoskeleton, transcription factor, and G-protein modulator. Pathway analysis revealed that cytoskeletal regulation by the Rho GTPase pathway, the Wnt pathway, the G-protein pathway, and the P53 pathway were affected by FMNL2. Many of these genes are in functional networks associated with cell proliferation, metastasis, Wnt or the Rho signalling pathway involved in the regulation of FMNL2. The expression of five differentially expressed genes including CXXC4, CD200, VAV1, CSF1, and EPHA2 was validated by real-time PCR and western blot analysis. Thus, FMNL2 is a positive regulator of cell motility, invasion, and metastasis of colorectal carcinoma.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.
authors.forename: Xi-Ling
authors.initials: XL
authors.lastname: Zhu
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Zeng
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.forename: Yu-Fa
authors.initials: YF
authors.lastname: Li
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Deng
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Liang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000080865:Formins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: C476208:FMNL2 protein, human; D000080865:Formins; D009363:Neoplasm Proteins; D011506:Proteins