title: Akt phosphorylates Prohibitin 1 to mediate its mitochondrial localization and promote proliferation of bladder cancer cells.
abstract: Bladder cancer (BC) is very common and associated with significant morbidity and mortality, though the molecular underpinnings of its origination and progression remain poorly understood. In this study, we demonstrate that Prohibitin 1 (PHB) was overexpressed in human BC tissues and that PHB upregulation was associated with poor prognosis. We also found that PHB was necessary and sufficient for BC cell proliferation. Interestingly, the overexpressed PHB was primarily found within mitochondria, and we provide the first direct evidence that phosphorylation by Akt at Thr258 of PHB induces this mitochondrial localization. Inhibiton of Akt reverses these effects and inhibited the proliferation of BC cells. Finally, the phosphorylation of PHB was required for BC cell proliferation, further implicating the importance of the Akt in BC. Taken together, these findings identify the Akt/PHB signaling cascade as a novel mechanism of cancer cell proliferation and provide the scientific basis for the establishment of PHB as a new prognostic marker and treatment target for BC.
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: P
authors.initials: P
authors.lastname: Dong
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liao
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: S
authors.initials: S
authors.lastname: Guo
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: S
authors.initials: S
authors.lastname: Mai
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: D
authors.initials: D
authors.lastname: Xie
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong 510060, China [2] Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation; D000091402:Prohibitins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; D051057:Proto-Oncogene Proteins c-akt