Cited by 199Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerProstate Cancer Treatment and Research

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PTEN Deficiency and AMPK Activation Promote Nutrient Scavenging and Anabolism in Prostate Cancer Cells

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Kim, Seong M., Nguyen, Tricia T., Ravi, Archna, Kubiniok, Peter, Finicle, Brendan T., Jayashankar, Vaishali, Malacrida, Leonel, Hou, Jue, Robertson, Jane, Gao, Dong, Chernoff, Jonathan, Digman, Michelle A., Potma, Eric O., Tromberg, Bruce J., Thibault, Pierre, Edinger, Aimee L.·2018·Cancer Discovery

DOI 10.1158/2159-8290.cd-17-1215PMC PMC6030497

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Abstract

We report that PTEN-deficient prostate cancer cells use macropinocytosis to survive and proliferate under nutrient stress.PTEN loss increased macropinocytosis only in the context of AMPK activation revealing a general requirement for AMPK in macropinocytosis and a novel mechanism by which AMPK promotes survival under stress.In prostate cancer cells, albumin uptake did not require macropinocytosis, but necrotic cell debris proved a specific macropinocytic cargo.Isotopic labeling confirmed that macropinocytosed necrotic cell proteins fueled new protein synthesis in prostate cancer cells.Supplementation with necrotic debris, but not albumin, also maintained lipid stores suggesting that macropinocytosis can supply nutrients other than amino acids.Non-transformed prostatic epithelial cells were not macropinocytic, but patient-derived prostate cancer organoids and xenografts and autochthonous prostate tumors all exhibited constitutive macropinocytosis, and blocking macropinocytosis limited prostate tumor growth.Macropinocytosis of extracellular material by prostate cancer cells is a previously unappreciated tumor-microenvironment interaction that could be targeted therapeutically.

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Authors: Kim, S. M., Nguyen, T. T., Ravi, A., Kubiniok, P., Finicle, B. T., Jayashankar, V., Malacrida, L., Hou, J., Robertson, J., Gao, D., Chernoff, J., Digman, M. A., Potma, E. O., Tromberg, B. J., Thibault, P., & Edinger, A. L.
Affiliations: University of California, Irvine (US)
Université de Montréal (CA)
Universidad de la República de Uruguay (UY)
Chinese Academy of Sciences (CN)
Fox Chase Cancer Center (US)
ORCID: Kim, Seong M.
Nguyen, Tricia T.
Kubiniok, Peter
Finicle, Brendan T.
Malacrida, Leonel
Hou, Jue
Gao, Dong
Chernoff, Jonathan
Digman, Michelle A.
Potma, Eric O.
Tromberg, Bruce J.
Thibault, Pierre
Edinger, Aimee L.
Venue: Cancer Discovery
Publisher: American Association for Cancer Research (AACR)
Published: 2018-03-23
Volume: 8
Issue: 7
Pages: 866-883
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-17-1215
PMC: PMC6030497
OpenAlex: W2789786349
Cited by: 199
References: 70
Citations by year: 2026: 9 · 2025: 20 · 2024: 28 · 2023: 27 · 2022: 30 · 2021: 31 · 2020: 19 · 2019: 20 · 2018: 15
FWCI: 7.56
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Discovery (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: HHS | National Institutes of Health (NIH) (GM089919, P30 CA62203, P41EB015890, P41-RR03155, P50-GM076516)
Canada Research Chairs (Chaires de recherche du Canada)
Genome Canada (Génome Canada)
canada National Science and engineering research council (311598)
Vanier Scholarship
DOD | Congressionally Directed Medical Research Programs (CDMRP) (W81XWH-11-1-0535)
American Cancer Society (ACS) (RSG-11-111-01-CDD)
University of california cancer research coordinating committee (CRR-17-426826)
UCI Applied Innovation (NA)
US Department of Education (GAANN P200A120207)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Keywords: PTEN loss, AMPK activation, prostate cancer, nutrient scavenging, anabolism, cancer metabolism
MeSH terms: Nutrients, Animals, Humans, Male, Mice, Inbred C57BL, Pinocytosis, Prostatic Neoplasms, Stress, Physiological, Gene Deletion, PTEN Phosphohydrolase, Mice, AMP-Activated Protein Kinases

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PTEN Deficiency and AMPK Activation Promote Nutrient Scavenging and Anabolism in Prostate Cancer Cells

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