title: IGF1/IGF1R/STAT3 signaling-inducible IFITM2 promotes gastric cancer growth and metastasis.
abstract: Interferon-induced transmembrane proteins (IFITMs) are expressed in some types of cancer. However, their precise roles in tumor progression remain unclear. The present study investigated the function of IFITM2 in gastric cancer (GC) progression. A retrospective analysis of a public database and 167 GC patients revealed that IFITM2 expression was upregulated in gastric tumor samples, which was positively correlated with disease progression, more frequent postoperative recurrence, and higher mortality rate. IFITM2 knockdown decreased GC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro. We also found that IFITM2 expression was in part induced by insulin-like growth factor (IGF) 1 via IGF1 receptor/signal transducer and activator of transcription 3 signaling. Furthermore, IFITM2 regulated interleukin-6 expression and secretion, which in turn increased IFITM2 expression. Silencing of IFITM2 expression suppressed tumor growth and lung metastasis in vivo. These results suggest that IFITM2 is a novel prognostic biomarker and regulator of GC progression.
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Lezhong
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Huanrong
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Minyu
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Changqie
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
authors.affiliation: Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: nfyyliaowj@163.com.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Liao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016208:Databases, Factual; D018450:Disease Progression; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D034622:RNA Interference; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C080081:IFITM2 protein, human; C583557:IGF1 protein, human; C000597236:IGF1R protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008565:Membrane Proteins; D017451:Receptors, Somatomedin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: EMT; Gastric cancer; IGF1/IGF1R/STAT3; IL-6; Interferon-induced transmembrane protein 2