title: Silencing of MICAL-L2 suppresses malignancy of ovarian cancer by inducing mesenchymal-epithelial transition.
abstract: Ovarian cancer remains the disease with the highest associated mortality rate of gynecologic malignancy due to cancer metastasis. Rearrangement of actin cytoskeleton by cytoskeleton protein plays a critical role in tumor cell metastasis. MICAL-L2, a member of MICAL family, can interact with actin-binding proteins, regulate actin cross-linking and coordinate the assembly of adherens junctions and tight junctions. However, the roles of MICAL-L2 in tumors and diseases have not been explored. In this study, we found that MICAL-L2 protein is significantly up-regulated in ovarian cancer tissues along with FIGO stage and associated with histologic subgroups of ovarian cancer. Silencing of MICAL-L2 suppressed ovarian cancer cell proliferation, migration and invasion ability. Moreover, silencing of MICAL-L2 prevented nuclear translocation of β-catenin, inhibited canonical wnt/β-catenin signaling and induced the mesenchymal-epithelial transition (MET). Taken together, our data indicated that MICAL-L2 may be an important regulator of epithelial-mesenchymal transition (EMT) in ovarian cancer cells and a new therapeutic target for interventions against ovarian cancer invasion and metastasis.
authors: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China; Department of Obstetrics and Gynecology, Ningbo First Hospital, Ninbo, Zhejiang 3015000, China.
authors: Lin-Yan
authors: LY
authors: Zhu
authors: Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors: Wen-Ming
authors: WM
authors: Zhang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors: Xiao-Mei
authors: XM
authors: Yang
authors: Department of Obstetrics and Gynecology, Ningbo First Hospital, Ninbo, Zhejiang 3015000, China.
authors: Lining
authors: L
authors: Cui
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors: Jun
authors: J
authors: Li
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors: Yan-Li
authors: YL
authors: Zhang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors: Ya-Hui
authors: YH
authors: Wang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors: Jun-Ping
authors: JP
authors: Ao
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors: Ming-Ze
authors: MZ
authors: Ma
authors: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China.
authors: Huan
authors: H
authors: Lu
authors: Department of Obstetrics and Gynecology, Changzhou Maternal and Child Care Hospital, Changzhou, Jiangsu 213003, China.
authors: Yuan
authors: Y
authors: Ren
authors: Department of Obstetrics and Gynecology, Changzhou Maternal and Child Care Hospital, Changzhou, Jiangsu 213003, China.
authors: Shao-Hua
authors: SH
authors: Xu
authors: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China.
authors: Guang-Dong
authors: GD
authors: Yang
authors: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China.
authors: Wei-Wei
authors: WW
authors: Song
authors: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China.
authors: Jing-Hao
authors: JH
authors: Wang
authors: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China.
authors: Xiao-Dan
authors: XD
authors: Zhang
authors: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China. Electronic address: rongzhang1965@163.com.
authors: Rong
authors: R
authors: Zhang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China. Electronic address: zzhang@shsci.org.
authors: Zhi-Gang
authors: ZG
authors: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C528177:MICALL2 protein, human; D008840:Microfilament Proteins; D051176:beta Catenin
keywords: EMT; Invasion; MICAL-L2; Ovarian cancer; Proliferation