Cholesterol-Dependent LRRC8A-Caveolin-1 Axis Sustains Pancreatic Cancer Growth
This is a preview of subscription content, access via your institution Prices may be subject to local taxes which are calculated during checkout The data supporting the findings of this study are available within the article and its Supplementary Information files, and all other relevant data are available from the corresponding author upon reasonable request. The RNA-sequencing data have been deposited in the GEO database under accession number GSE319713. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12–49. Rahib L, Wehner MR, Matrisian LM, Nead KT. Estimated Projection of US Cancer Incidence and Death to 2040. JAMA Netw Open. 2021;4:e214708. Lansbergen MF, Dings MPG, Manoukian P, Fariña A, Waasdorp C, Hooijer GKJ, et al. Transcriptome-based classification to predict FOLFIRINOX response in a real-world metastatic pancreatic cancer cohort. Transl Res. 2024;273:137–47. Murphy SJ, Hart SN, Lima JF, Kipp BR, Klebig M, Winters JL, et al. Genetic Alterations Associated With Progression From Pancreatic Intraepithelial Neoplasia to Invasive Pancreatic Tumor. Gastroenterology. 2013;145:1098–1109.e1. Karamitopoulou E. Tumour microenvironment of pancreatic cancer: immune landscape is dictated by molecular and histopathological features. Br J Cancer. 2019;121:5–14. Encarnación-Rosado J, Kimmelman AC. Harnessing metabolic dependencies in pancreatic cancers. Nat Rev Gastroenterol Hepatol. 2021;18:482–92. Grant TJ, Hua K, Singh A. Molecular Pathogenesis of Pancreatic Cancer. Prog Mol Biol Transl Sci. 2016;144:241–75. Commisso C, Davidson SM, Soydaner-Azeloglu RG, Parker SJ, Kamphorst JJ, Hackett S, et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature. 2013;497:633–7. Zhang Z, Zhang H, Liao X, Tsai H. KRAS mutation: The booster of pancreatic ductal adenocarcinoma transformation and progression. Front Cell Dev Biol. 2023;11:1147676. Delpire E, Gagnon KB. Water Homeostasis and Cell Volume Maintenance and Regulation. Curr Top Membr. 2018;81:3–52. Hoffmann EK, Lambert IH, Pedersen SF. Physiology of Cell Volume Regulation in Vertebrates. Physiol Rev. 2009;89:193–277. Chen L, König B, Liu T, Pervaiz S, Razzaque YS, Stauber T. More than just a pressure release valve: physiological roles of volume-regulated LRRC8 anion channels. Biol Chem. 2019;400:1481–96. Lloyd AC. The Regulation of Cell Size. Cell. 2013;154:1194–205. Qiu Z, Dubin AE, Mathur J, Tu B, Reddy K, Miraglia LJ, et al. SWELL1, a Plasma Membrane Protein, Is an Essential Component of Volume-Regulated Anion Channel. Cel
New research has uncovered a cholesterol-dependent axis involving LRRC8A and caveolin-1 that plays a crucial role in sustaining KRAS/EGFR signaling, ribosome biogenesis, and overall growth in pancreatic ductal adenocarcinoma. This finding sheds light on the molecular mechanisms driving pancreatic cancer progression. The identified axis represents a potential therapeutic target for intervention. Understanding this pathway is vital for developing more effective treatments for this aggressive form of cancer. The study details specific molecular interactions that promote tumor development. This research contributes to the ongoing effort to combat pancreatic cancer.
This scientific discovery identifies a key molecular pathway driving pancreatic cancer growth, offering potential new targets for therapeutic intervention.
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