Starving PTEN-deficient prostate cancer cells thrive under nutrient stress by scavenging corpses for their supper

Vaishali Jayashankar; Brendan T Finicle; Aimee L Edinger

doi:10.1080/23723556.2018.1472060

Starving PTEN-deficient prostate cancer cells thrive under nutrient stress by scavenging corpses for their supper

Mol Cell Oncol. 2018 Aug 17;5(4):e1472060. doi: 10.1080/23723556.2018.1472060. eCollection 2018.

Authors

Vaishali Jayashankar¹, Brendan T Finicle¹, Aimee L Edinger¹

Affiliation

¹ Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.

Abstract

Our recent work demonstrates that inactivating mutations in phosphatase and tensin homolog (PTEN) are sufficient to drive macropinocytosis in the context of AMP-activated protein kinase (AMPK) activation. Given that blocking macropinocytosis limits PTEN-deficient prostate tumor growth, AMPK or phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors could have therapeutic value in castration-resistant prostate cancer patients, particularly when used in combination with standard of care therapies. Abbreviations: ATG5: autophagy related 5; NHE: Na(+)/H(+) exchanger; PAK1: p21-activated kinase 1; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; PIP₃: phosphatidylinositol (3,4,5)-trisphosphate; PIP₂: phosphatidylinositol (4,5)-bisphosphate; RAC1: Rac family small GTPase 1.

Keywords: AMPK; PI3K pathway; PTEN; macropinocytosis; necrosis; nutrient scavenging; prostate cancer.

Grants and funding

This work was supported by grants to ALE from the NIH (R01 GM089919), CDMRP (W81XWH-1-0535), American Cancer Society (RSG-11-111-01-CDD), University of California Cancer Research Coordinating Committee (CRR-17-426826) and UCI Applied Innovation.