ArticleNature communications2024
Cell polarity proteins promote macropinocytosis in response to metabolic stress.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Beyond the scaffold: extracellular matrix uptake in breast cancer.Biochemical Society transactions · 2026Review
- Exploiting Macropinocytosis Drives Redox Vulnerability to Preferentially Target Drug-Resistant Cancer.ACS nano · 2026Article
- Ceramide-PKCζ signaling axis mediates burn-enhanced ectopic calcification during Achilles tendon healing.Journal of molecular histology · 2026Article
- Pictilisib and nutrient stress synergize to induce methuosis via PI(4,5)PCell death & disease · 2026Article
- Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.Experimental hematology & oncology · 2026Review
- Ras promotes macropinocytic nutrient uptake by suppressing the albumin recycling receptor FcRn.EMBO reports · 2026Article
- Mechanism analysis of transgene expression induced by chitosan/hyaluronic acid nanoparticles in CD44v9/RHAMM co-expressed gastric cancer cells: contribution of hyaluronic acid to RHAMM-mediated intracellular transport.Glycoconjugate journal · 2026Article
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
- Macropinocytosis mediates neurotropism ofResearch square · 2025Article
- Gut commensal Bifidobacterium-derived extracellular vesicles modulate the therapeutic effects of anti-PD-1 in lung cancer.Nature communications · 2025Article
- Targeting Wnt-driven metabolic adaptations in cancer: integrating glycolysis, glutaminolysis, IDO1-mediated immune evasion, and therapeutic delivery strategies.Frontiers in cell and developmental biology · 2025Review
- Macropinocytosis mediates resistance to loss of glutamine transport in triple-negative breast cancer.The EMBO journal · 2024Article
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11 authors.
Funding
Abstract
Macropinocytosis has emerged as a scavenging pathway that cancer cells exploit to survive in a nutrient-deprived microenvironment. Tumor cells are especially reliant on glutamine for their survival, and in pancreatic ductal adenocarcinoma (PDAC) cells, glutamine deficiency can enhance the stimulation of macropinocytosis. Here, we identify the atypical protein kinase C (aPKC) enzymes, PKCζ and PKCι, as regulators of macropinocytosis. In normal epithelial cells, aPKCs associate with the scaffold proteins Par3 and Par6 to regulate cell polarity, affecting several targets, including the Par1 kinases and we find that each of these proteins is required for macropinocytosis. Mechanistically, aPKCs are regulated by EGFR signaling or by the transcription factor CREM to promote the Par3 relocation to microtubules, facilitating macropinocytosis in a dynein-dependent manner. Importantly, cell fitness impairment caused by aPKC depletion is rescued by the restoration of macropinocytosis and aPKCs support PDAC growth in vivo. Our findings enhance our understanding of the mechanistic underpinnings that control macropinocytic uptake in the context of metabolic stress.
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