[HTML][HTML] Akt phosphorylates Prohibitin 1 to mediate its mitochondrial localization and promote proliferation of bladder cancer cells

L Jiang, P Dong, Z Zhang, C Li, Y Li, Y Liao, X Li… - Cell death & …, 2015 - nature.com
L Jiang, P Dong, Z Zhang, C Li, Y Li, Y Liao, X Li, Z Wu, S Guo, S Mai, D Xie, Z Liu, F Zhou
Cell death & disease, 2015nature.com
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 …
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.
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