title: FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer.
abstract: Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. In the current study, we found family with sequence similarity 83, member A (FAM83A) is significantly overexpressed and associated with poorer overall survival and disease-free survival in pancreatic cancer. Overexpression of FAM83A markedly promoted, whereas inhibition of FAM83A decreased, CSC-like traits and chemoresistance both in vitro and in an in vivo mouse model of pancreatic cancer. Furthermore, overexpression of FAM83A activated the well-characterized CSC-associated pathways transforming growth factor-β (TGF-β) signaling and Wnt/β-catenin signaling. Importantly, the FAM83A locus was amplified in a number of human cancers and silencing FAM83A in associated cancer cell lines inhibited activation of the WNT/β-catenin and TGF-β signaling pathways and reduced tumorigenicity. Taken together, these results indicate that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target.
authors.affiliation: Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Emergency Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jin