| First Author | Reina-Campos M | Year | 2019 |
| Journal | Cancer Cell | Volume | 35 |
| Issue | 3 | Pages | 385-400.e9 |
| PubMed ID | 30827887 | Mgi Jnum | J:273246 |
| Mgi Id | MGI:6285465 | Doi | 10.1016/j.ccell.2019.01.018 |
| Citation | Reina-Campos M, et al. (2019) Increased Serine and One-Carbon Pathway Metabolism by PKClambda/iota Deficiency Promotes Neuroendocrine Prostate Cancer. Cancer Cell 35(3):385-400.e9 |
| abstractText | Increasingly effective therapies targeting the androgen receptor have paradoxically promoted the incidence of neuroendocrine prostate cancer (NEPC), the most lethal subtype of castration-resistant prostate cancer (PCa), for which there is no effective therapy. Here we report that protein kinase C (PKC)lambda/iota is downregulated in de novo and during therapy-induced NEPC, which results in the upregulation of serine biosynthesis through an mTORC1/ATF4-driven pathway. This metabolic reprogramming supports cell proliferation and increases intracellular S-adenosyl methionine (SAM) levels to feed epigenetic changes that favor the development of NEPC characteristics. Altogether, we have uncovered a metabolic vulnerability triggered by PKClambda/iota deficiency in NEPC, which offers potentially actionable targets to prevent therapy resistance in PCa. |
