Macropinocytosis in Cancer-Associated Fibroblasts Is Dependent on CaMKK2/ARHGEF2 Signaling and Functions to Support Tumor and Stromal Cell Fitness.

Animals Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism Cancer-Associated Fibroblasts Carcinoma, Pancreatic Ductal / metabolism Humans Mice Mice, Inbred C57BL Pancreatic Neoplasms / metabolism Pinocytosis Rho Guanine Nucleotide Exchange Factors / metabolism Signal Transduction Stromal Cells Tumor Microenvironment

Journal

Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693

Informations de publication

Date de publication:
07 2021
Historique:
received: 29 01 2020
revised: 15 01 2021
accepted: 26 02 2021
pubmed: 4 3 2021
medline: 1 3 2022
entrez: 3 3 2021
Statut: ppublish

Résumé

Although pancreatic ductal adenocarcinoma (PDAC) cells are exposed to a nutrient-depleted tumor microenvironment, they can acquire nutrients via macropinocytosis, an endocytic form of protein scavenging that functions to support cancer metabolism. Here, we provide evidence that macropinocytosis is also operational in the pancreatic tumor stroma. We find that glutamine deficiency triggers macropinocytic uptake in pancreatic cancer-associated fibroblasts (CAF). Mechanistically, we decipher that stromal macropinocytosis is potentiated via the enhancement of cytosolic Ca

Identifiants

DOI: 10.1158/2159-8290.CD-20-0119 PMID: 33653692 PMC: PMC8292164
pubmed: 33653692
pii: 2159-8290.CD-20-0119
doi: 10.1158/2159-8290.CD-20-0119
pmc: PMC8292164
mid: NIHMS1681606
doi:

Substances chimiques

ARHGEF2 protein, human 0
Rho Guanine Nucleotide Exchange Factors 0
Calcium-Calmodulin-Dependent Protein Kinase Kinase EC 2.7.11.17

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1808-1825

Subventions

Organisme : NCI NIH HHS
ID : R01 CA207189
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA030199
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA254806
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA211036
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA243701
Pays : United States

Informations de copyright

©2021 American Association for Cancer Research.

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Auteurs

Yijuan Zhang (Y)

Cell and Molecular Biology of Cancer Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

M Victoria Recouvreux (MV)

Cell and Molecular Biology of Cancer Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

Michael Jung (M)

Cell and Molecular Biology of Cancer Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

Koen M O Galenkamp (KMO)

Cell and Molecular Biology of Cancer Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
ORCID: 0000-0001-7220-6516

Yunbo Li (Y)

Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California.

Olga Zagnitko (O)

Cancer Metabolism Core Resource, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

David A Scott (DA)

Cancer Metabolism Core Resource, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
ORCID: 0000-0002-8668-2449

Andrew M Lowy (AM)

Moores Cancer Center, University of California, San Diego, La Jolla, California.
Division of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, California.
ORCID: 0000-0002-7106-0735

Cosimo Commisso (C)

Cell and Molecular Biology of Cancer Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. ccommisso@sbpdiscovery.org.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Calcium-Calmodulin-Dependent Protein Kinases › Calcium-Calmodulin-Dependent Protein Kinase Kinase › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Fibroblastes associés au cancer › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Endocytose › Pinocytose › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Régulateurs des protéines G › Facteurs d'échange de nucléotides guanyliques › Rho guanine nucleotide exchange factors › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Cellules stromales › Macropinocytosis in Cancer-Associated...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Macropinocytosis in Cancer-Associated...