title: FAT10, an ubiquitin-like protein, confers malignant properties in non-tumorigenic and tumorigenic cells.
abstract: FAT10 (HLA-F-adjacent transcript 10) is an ubiquitin-like modifier, which has been implicated in immune response and cancer development. In particular, the hypothesis of FAT10 as a mediator of tumorigenesis stems from its ability to associate with a spindle checkpoint protein Mad2 during mitosis and cause aneuploidy, a hallmark of cancer cells. Furthermore, FAT10 is overexpressed in several carcinomas types, including that of liver and colon. Nevertheless, direct evidence linking FAT10 to cell malignant transformation and progression is lacking. Here, we demonstrate that high FAT10 expression enhanced the proliferative, invasive, migratory and adhesive functions of the transformed cell line, HCT116. These observations were consistently demonstrated in an immortalized, non-tumorigenic liver cell line NeHepLxHT. Importantly, FAT10 can induce malignant transformation as evidenced from the anchorage-independent growth as well as in vivo tumor-forming abilities of FAT10-overexpressing NeHepLxHT cells, whereas in rapidly proliferating HCT116, increased FAT10 further augmented tumor growth. FAT10 was found to activate nuclear factor-κB (NFκB), which in turn upregulated the chemokine receptors CXCR4 and CXCR7. Importantly, small interfering RNA depletion of CXCR7 and CXCR4 attenuated cell invasion of FAT10-overexpressing cells, indicating that the CXCR4/7 is crucial for the FAT10-dependent malignant phenotypes. Taken together, our data reveal novel functions of FAT10 in malignant transformation and progression, via the NFκB-CXCR4/7 pathway.
authors: Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, Singapore.
authors: Yun
authors: Y
authors: Gao
authors: Steven Setiawan
authors: SS
authors: Theng
authors: Jingli
authors: J
authors: Zhuo
authors: Wei Bing
authors: WB
authors: Teo
authors: Jianwei
authors: J
authors: Ren
authors: Caroline G L
authors: CG
authors: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014452:Ubiquitins / Q000378:metabolism / Q000502:physiology*
chemical_list: D017931:DNA Primers; C109184:UBD protein, human; D014452:Ubiquitins