التفاصيل البيبلوغرافية
| العنوان: |
Cell polarity proteins promote macropinocytosis in response to metabolic stress. |
| المؤلفون: |
Lambies G, Lee SW, Duong-Polk K, Aza-Blanc P, Maganti S, Dawson DW, Commisso C |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 30. Date of Electronic Publication: 2024 Jan 30. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Macropinocytosis has emerged as a nutrient-scavenging pathway that cancer cells exploit to survive the nutrient-deprived conditions of the tumor microenvironment. Cancer cells are especially reliant on glutamine for their survival, and in pancreatic ductal adenocarcinoma (PDAC) cells, glutamine deficiency can enhance the stimulation of macropinocytosis, allowing the cells to escape metabolic stress through the production of extracellular-protein-derived amino acids. Here, we identify the atypical protein kinase C (aPKC) enzymes, PKCζ and PKCι as novel regulators of macropinocytosis. In normal epithelial cells, aPKCs are known to regulate cell polarity in association with the scaffold proteins Par3 and Par6, controlling the function of several targets, including the Par1 kinases. In PDAC cells, we identify that each of these cell polarity proteins are required for glutamine stress-induced macropinocytosis. Mechanistically, we find that the aPKCs are regulated by EGFR signaling or by the transcription factor CREM to promote the relocation of Par3 to microtubules, facilitating macropinocytosis in a dynein-dependent manner. Importantly, we determine that cell fitness impairment caused by aPKC depletion is rescued by the restoration of macropinocytosis and that aPKCs support PDAC growth in vivo. These results identify a previously unappreciated role for cell polarity proteins in the regulation of macropinocytosis and provide a better understanding of the mechanistic underpinnings that control macropinocytic uptake in the context of metabolic stress. |
| تواريخ الأحداث: |
Date Created: 20240131 Latest Revision: 20240131 |
| رمز التحديث: |
20240131 |
| مُعرف محوري في PubMed: |
PMC10827152 |
| DOI: |
10.1101/2024.01.16.575943 |
| PMID: |
38293142 |
| قاعدة البيانات: |
MEDLINE |
