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Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis.
Cell ; 152(3): 599-611, 2013 Jan 31.
Article en En | MEDLINE | ID: mdl-23374352
ABSTRACT
Tumor cells have high-energetic and anabolic needs and are known to adapt their metabolism to be able to survive and keep proliferating under conditions of nutrient stress. We show that PKCζ deficiency promotes the plasticity necessary for cancer cells to reprogram their metabolism to utilize glutamine through the serine biosynthetic pathway in the absence of glucose. PKCζ represses the expression of two key enzymes of the pathway, PHGDH and PSAT1, and phosphorylates PHGDH at key residues to inhibit its enzymatic activity. Interestingly, the loss of PKCζ in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, whereas patients with low levels of PKCζ have a poor prognosis. Furthermore, PKCζ and caspase-3 activities are correlated with PHGDH levels in human intestinal tumors. Taken together, this demonstrates that PKCζ is a critical metabolic tumor suppressor in mouse and human cancer.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteína Quinasa C / Adenocarcinoma / Adenoma / Neoplasias del Colon Límite: Animals / Humans Idioma: En Año: 2013 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteína Quinasa C / Adenocarcinoma / Adenoma / Neoplasias del Colon Límite: Animals / Humans Idioma: En Año: 2013 Tipo del documento: Article