AXL Is a Key Factor for Cell Plasticity and Promotes Metastasis in Pancreatic Cancer.

Autor:	Du W; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.; Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, Texas., Phinney NZ; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.; Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, Texas., Huang H; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas., Wang Z; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas., Westcott J; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas., Toombs JE; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas., Zhang Y; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.; Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, Texas., Beg MS; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas., Wilkie TM; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas., Lorens JB; Department of Biomedicine, Centre for Cancer Biomarkers, Norwegian Centre of Excellence, University of Bergen, Bergen, Norway., Brekken RA; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas. rolf.brekken@utsouthwestern.edu.; Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, Texas.; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2021 Aug; Vol. 19 (8), pp. 1412-1421. Date of Electronic Publication: 2021 Apr 02.
DOI:	10.1158/1541-7786.MCR-20-0860
Abstrakt:	Pancreatic ductal adenocarcinoma (PDA), a leading cause of cancer-related death in the United States, has a high metastatic rate, and is associated with persistent immune suppression. AXL, a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family, is a driver of metastasis and immune suppression in multiple cancer types. Here we use single-cell RNA-sequencing to reveal that AXL is expressed highly in tumor cells that have a mesenchymal-like phenotype and that AXL expression correlates with classic markers of epithelial-to-mesenchymal transition. We demonstrate that AXL deficiency extends survival, reduces primary and metastatic burden, and enhances sensitivity to gemcitabine in an autochthonous model of PDA. PDA in AXL-deficient mice displayed a more differentiated histology, higher nucleoside transporter expression, and a more active immune microenvironment compared with PDA in wild-type mice. Finally, we demonstrate that AXL-positive poorly differentiated tumor cells are critical for PDA progression and metastasis, emphasizing the potential of AXL as a therapeutic target in PDA. IMPLICATIONS: These studies implicate AXL as a marker of undifferentiated PDA cells and a target for therapy. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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