title: Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway.
abstract: Our previous work identified thioredoxin-like protein 2 (Txl-2), a novel thioredoxin family member, as the target of the monoclonal antibody MC3 which can detect colon cancer with high sensitivity and specificity. In the present study, the function of the most abundant isoform Txl-2b in cell proliferation and apoptosis was investigated. Txl-2 overexpression correlated with increased clinical stages. Inhibition of Txl-2b suppressed cell proliferation, induced cell cycle arrest at the G1/S phase, and led to responsiveness to the vincristine-induced apoptosis in SW620 cells. Txl-2b overexpression in LoVo cells had the opposite effect, which was dependent on Trx domain function. In vivo studies validated that Txl-2b expression promoted colon cancer tumorigenesis in nude mice. Further studies revealed that nuclear factor-κB (NF-κB) signaling was activated by Txl-2b. Inhibition of NF-κB activation partly abrogated the pro-proliferation and anti-apoptotic phenotypes mediated by Txl-2b via reduced Cyclin D1, Bcl-2, Bcl-xL and Survivin expression and increased Caspase-3 activation. Overall, our results indicate that Txl-2b expression stimulates cancer cell proliferation, accelerates the cell cycle and contributes to apoptosis resistance in colon cancer and provides a potential therapeutic target for colon cancer treatment.
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Guanhong
authors.initials: G
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Gaofei
authors.initials: G
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China. Electronic address: wangx@fmmu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China. Electronic address: daimingfan@fmmu.edu.cn.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D009367:Neoplasm Staging; D015398:Signal Transduction; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C404105:GLRX3 protein, human; D016328:NF-kappa B; D019938:Cyclin D1; D013879:Thioredoxins
keywords: Apoptosis; Colon cancer; NF-κB; Proliferation; Thioredoxin-like 2