title: XB130 mediates cancer cell proliferation and survival through multiple signaling events downstream of Akt.
abstract: XB130, a novel adaptor protein, mediates RET/PTC chromosome rearrangement-related thyroid cancer cell proliferation and survival through phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway. Recently, XB130 was found in different cancer cells in the absence of RET/PTC. To determine whether RET/PTC is required of XB130-related cancer cell proliferation and survival, WRO thyroid cancer cells (with RET/PTC mutation) and A549 lung cancer cells (without RET/PTC) were treated with XB130 siRNA, and multiple Akt down-stream signals were examined. Knocking-down of XB130 inhibited G(1)-S phase progression, and induced spontaneous apoptosis and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Knocking-down of XB130 reduced phosphorylation of p21Cip1/WAF1, p27Kip1, FOXO3a and GSK3β, increased p21Cip1/WAF1protein levels and cleavages of caspase-8 and-9. However, the phosphorylation of FOXO1 and the protein levels of p53 were not affected by XB130 siRNA. We also found XB130 can be phosphorylated by multiple protein tyrosine kinases. These results indicate that XB130 is a substrate of multiple protein tyrosine kinases, and it can regulate cell proliferation and survival through modulating selected down-stream signals of PI3K/Akt pathway. XB130 could be involved in growth and survival of different cancer cells.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Research Institute, Toronto, Ontario, Canada.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Grace
authors.initials: G
authors.lastname: Shen-Tu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iitaka
authors.forename: Valentina
authors.initials: V
authors.lastname: De Falco
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014178:Translocation, Genetic
chemical_list: C521126:AFAP1L2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt