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

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:

• macropinocytosis
• nutrient scavenging
• prostate cancer
• PTEN
• PI3K pathway
• AMPK
• necrosis

Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Additional information

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.