title: Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis.
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.
authors: Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Li
authors: L
authors: Ma
authors: Yongzhen
authors: Y
authors: Tao
authors: Angeles
authors: A
authors: Duran
authors: Victoria
authors: V
authors: Llado
authors: Anita
authors: A
authors: Galvez
authors: Jennifer F
authors: JF
authors: Barger
authors: Elias A
authors: EA
authors: Castilla
authors: Jing
authors: J
authors: Chen
authors: Tomoko
authors: T
authors: Yajima
authors: Aleksey
authors: A
authors: Porollo
authors: Mario
authors: M
authors: Medvedovic
authors: Laurence M
authors: LM
authors: Brill
authors: David R
authors: DR
authors: Plas
authors: Stefan J
authors: SJ
authors: Riedl
authors: Michael
authors: M
authors: Leitges
authors: Maria T
authors: MT
authors: Diaz-Meco
authors: Adam D
authors: AD
authors: Richardson
authors: Jorge
authors: J
authors: Moscat
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053898:Biosynthetic Pathways; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D012694:Serine / Q000096:biosynthesis; D013047:Specific Pathogen-Free Organisms; D013312:Stress, Physiological
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D012694:Serine; C081975:protein kinase C eta; D011493:Protein Kinase C; D005947:Glucose
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