PHGDH heterogeneity potentiates cancer cell dissemination and metastasis.

ABSTRACT: Cancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs¹. Genetic, transcriptional and translational heterogeneity contributes to this dynamic process^2,3. Metabolic heterogeneity has also been observed⁴, yet its role in cancer progression is less explored. Here we find that the loss of phosphoglycerate dehydrogenase (PHGDH) potentiates metastatic dissemination. Specifically, we find that heterogeneous or low PHGDH expression in primary tumours of patients with breast cancer is associated with decreased metastasis-free survival time. In mice, circulating tumour cells and early metastatic lesions are enriched with Phgdh^low cancer cells, and silencing Phgdh in primary tumours incr

SUBMITTER: Rossi M 

PROVIDER: S-EPMC9888363 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature