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AXL Is a Key Factor for Cell Plasticity and Promotes Metastasis in Pancreatic Cancer.
Du, Wenting; Phinney, Natalie Z; Huang, Huocong; Wang, Zhaoning; Westcott, Jill; Toombs, Jason E; Zhang, Yuqing; Beg, Muhammad S; Wilkie, Thomas M; Lorens, James B; Brekken, Rolf A.
Affiliation
  • Du W; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.
  • Phinney NZ; 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; Cancer Biology Graduate Program, 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 Molecular Biology, 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.
  • Beg MS; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.
  • Wilkie TM; Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.
  • Lorens JB; Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, Texas.
  • Brekken RA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Mol Cancer Res ; 19(8): 1412-1421, 2021 08.
Article in En | MEDLINE | ID: mdl-33811159
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.
Subject(s)

Full text: 1 Database: MEDLINE Main subject: Pancreatic Neoplasms / Proto-Oncogene Proteins / Receptor Protein-Tyrosine Kinases / Carcinoma, Pancreatic Ductal / Cell Plasticity / Neoplasm Metastasis Type of study: Prognostic_studies Limits: Animals / Female / Humans / Male Language: En Year: 2021 Type: Article

Full text: 1 Database: MEDLINE Main subject: Pancreatic Neoplasms / Proto-Oncogene Proteins / Receptor Protein-Tyrosine Kinases / Carcinoma, Pancreatic Ductal / Cell Plasticity / Neoplasm Metastasis Type of study: Prognostic_studies Limits: Animals / Female / Humans / Male Language: En Year: 2021 Type: Article