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Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [nanoString nCounter]

ABSTRACT: Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [nanoString nCounter]

PROVIDER: PRJNA1283083 | ENA |

REPOSITORIES: ENA

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Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [nanoString nCounter]

Project description:Pancreatic ductal adenocarcinoma (PDAC) tumors are glutamine-deficient, and both tumor cells and cancer-associated fibroblasts (CAFs) rely on this amino acid to maintain fitness and induce macropinocytosis as an adaptive response. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive. In this study, we find that macropinocytosis sustains the myCAF phenotype under glutamine limitation by preventing inflammatory reprogramming. Our data demonstrate that metabolic stress induces an intrinsic inflammatory CAF (iCAF) program through MEK-ERK signaling. We find that blocking macropinocytosis in vivo promotes myCAF-to-iCAF transitions, remodeling the tumor stroma. Importantly, stromal remodeling driven by macropinocytosis inhibition—including iCAF enrichment, collagen reduction, immune cell infiltration, and vascular expansion—sensitizes PDAC tumors to immunotherapy and chemotherapy. Our findings reveal that inhibiting macropinocytosis promotes an inflammatory, less fibrotic tumor microenvironment that can be leveraged to improve therapeutic responses in PDAC.

2025-06-27 | GSE301021 | GEO

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [scRNA-seq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) tumors are deficient in glutamine, an amino acid that tumor cells and cancer-associated fibroblasts (CAFs) use to sustain their fitness. In PDAC, both cell types stimulate macropinocytosis as an adaptive response to glutamine depletion. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive. In this study, we find that macropinocytosis functions to control CAF subtype identity when glutamine is limiting. Our data demonstrate that metabolic stress leads to an intrinsic inflammatory CAF (iCAF) program driven by MEK/ERK signaling. Utilizing in vivo models, we find that blocking macropinocytosis triggers CAF subtype transitions and reorganizes the tumor stroma. Importantly, these changes in stromal architecture can be exploited to sensitize PDAC to immunotherapy and chemotherapy. Our findings demonstrate that metabolic stress plays a role in shaping the tumor microenvironment, and that this attribute can be harnessed for therapeutic impact.

2025-05-16 | GSE291120 | GEO

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [RNA-seq]

2025-05-16 | GSE291118 | GEO

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer

Project description:Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer

| PRJNA1232025 | ENA

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [RNA-seq]

Project description:Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [RNA-seq]

| PRJNA1232029 | ENA

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [scRNA-seq]

Project description:Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [scRNA-seq]

| PRJNA1232032 | ENA

nCounter NanoString Human Immunology V2 panel

Project description:nCounter NanoString Human Immunology V2 panel

| PRJNA751396 | ENA

Nanostring ncounter NHP Immunology V2 panel

Project description:Nanostring ncounter NHP Immunology V2 panel

| PRJNA792145 | ENA

NanoString nCounter Human HCC expression analysis

Project description:NanoString nCounter Human HCC expression analysis

| PRJNA488485 | ENA

Nanostring nCounter human miRNA assay (v1) of eosinophilic esophagitis

Project description:Nanostring nCounter Human miRNA assay (v1) of esophageal mucosal biopsies from children with eosinophilic esophagitis and controls Individual esophageal mucosal biopsies from children with eosinoniphilic esophagitis and controls were analysed for detection of microRNA

2014-09-01 | E-GEOD-55794 | biostudies-arrayexpress

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