title: TUSC3 promotes colorectal cancer progression and epithelial-mesenchymal transition (EMT) through WNT/β-catenin and MAPK signalling.
abstract: Colorectal cancer (CRC) is one of the most common malignancies and is the second leading cause of cancer death in humans. Tumour suppressor candidate 3 (TUSC3) plays an important role in embryogenesis and metabolism. Deletion of TUSC3 often causes non-syndromic mental retardation. Even though TUSC3 deregulation is frequently observed in epithelial cancers, the function of TUSC3 in CRC has remained unknown. In this study, we observed greater expression of TUSC3 at the mRNA and protein level in clinical colorectal tumour samples compared with paired normal tissues. Gain- and loss-of-function analyses were performed to evaluate the functional significance of TUSC3 in CRC initiation and progression. Immunoblotting, immunofluorescence, and co-immunoprecipitation analyses were used to identify potential pathways with which TUSC3 might be involved. Overexpression of TUSC3 in CRC cells induced epithelial-mesenchymal transition (EMT) in CRC cells, accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation, migration, and invasion, as well as accelerated xenograft tumour growth, were observed in TUSC3-overexpressing CRC cells, while opposite effects were achieved in TUSC3-silenced cells. In conclusion, our study demonstrated the oncogenic role of TUSC3 in CRC and showed that TUSC3 may be responsible for alternations in the proliferation ability, aggressiveness, and invasive/metastatic potential of CRC through regulating the MAPK, PI3K/Akt, and Wnt/β-catenin signalling pathways.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, 1838 Guangzhou Avenue, Guangzhou, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, 1838 Guangzhou Avenue, Guangzhou, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, 1838 Guangzhou Avenue, Guangzhou, PR China.
authors.forename: Kang
authors.initials: K
authors.lastname: Guo
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, 1838 Guangzhou Avenue, Guangzhou, PR China.
authors.forename: Weizhao
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, 1838 Guangzhou Avenue, Guangzhou, PR China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, 1838 Guangzhou Avenue, Guangzhou, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, 1838 Guangzhou Avenue, Guangzhou, PR China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou, PR China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, 1838 Guangzhou Avenue, Guangzhou, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000209:etiology*; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D008819:Mice, Nude; D008875:Middle Aged; D010641:Phenotype; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins
keywords: EMT; TUSC3 gene; colorectal cancer; invasion; metastasis