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The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming.

Liem PhanPing-Chieh ChouGuermarie Velazquez-TorresIsmael SamudioKenneth ParrenoYaling HuangChieh TsengThuy VuChris GullyChun-Hui SuEdward WangJian ChenHyun-Ho ChoiEnrique Fuentes-MatteiJi-Hyun ShinChristine ShiangBrian GrabinerMarzenna BlonskaStephen SkerlYiping ShaoDianna CodyJorge DelacerdaCharles KingsleyDouglas WebbColin CarlockZhongguo ZhouYun-Chih HsiehJaehyuk LeeAndrew ElliottMarc RamirezJames A BanksonJohn HazleYongxing WangLei LiShaofan WengNibal RizkYu Ye WenXin LinHua WangHuamin WangAijun ZhangXuefeng XiaYun WuMouhammed HabraWei YangLajos PusztaiSai-Ching YeungMong-Hong Lee
Published in: Nature communications (2015)
Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3σ opposes tumour-promoting metabolic programmes by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3σ demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3σ expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3σ is an important regulator of tumour metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3σ in tumours could be a promising direction for targeted anticancer metabolism therapy development in future.
Keyphrases
  • papillary thyroid
  • gene expression
  • cell cycle
  • squamous cell
  • poor prognosis
  • stem cells
  • cell proliferation
  • transcription factor
  • childhood cancer
  • cancer therapy
  • cell therapy
  • smoking cessation