title: AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer.
abstract: The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Divine
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Mai R
authors.initials: MR
authors.lastname: Nguyen
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Meller
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Riva A
authors.initials: RA
authors.lastname: Desai
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Batool
authors.initials: B
authors.lastname: Arif
authors.affiliation: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.|Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: Erinn B
authors.initials: EB
authors.lastname: Rankin
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Bligard
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Cherise
authors.initials: C
authors.lastname: Meyerson
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Hagemann
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Massad
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Premal H
authors.initials: PH
authors.lastname: Thaker
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Hagemann
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: McCourt
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Matt A
authors.initials: MA
authors.lastname: Powell
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.|Center for Reproductive Health Sciences (CRepHS), Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Fuh
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D016019:Survival Analysis; D015854:Up-Regulation; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D016326:Extracellular Matrix Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase
keywords: ARK1; AXL; MMP; endometrial cancer; uPA