title: Notch1 Pathway Activity Determines the Regulatory Role of Cancer-Associated Fibroblasts in Melanoma Growth and Invasion.
abstract: Cancer-associated fibroblasts (CAF) play a crucial role in regulating cancer progression, yet the molecular determinant that governs the tumor regulatory role of CAF remains unknown. Using a mouse melanoma model in which exogenous melanoma cells were grafted on the skin of two lines of mice where the genetic activation or inactivation of Notch1 signaling specifically occurs in natural host stromal fibroblasts, we demonstrated that Notch1 pathway activity could determine the tumor-promoting or tumor-suppressing phenotype in CAF. CAF carrying elevated Notch1 activity significantly inhibited melanoma growth and invasion, while those with a null Notch1 promoted melanoma invasion. These findings identify the Notch1 pathway as a molecular determinant that controls the regulatory role of CAF in melanoma skin growth and invasion, unveiling Notch1 signaling as a potential therapeutic target for melanoma and potentially other solid tumors.
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, Florida, United States of America.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, Florida, United States of America.|Department of Thoracic Surgery, the 2nd Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Kong
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, Florida, United States of America.
authors.forename: Massimiliano L
authors.initials: ML
authors.lastname: Ferrari
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland.
authors.forename: Freddy
authors.initials: F
authors.lastname: Radtke
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, Florida, United States of America.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Capobianco
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, Florida, United States of America.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D017353:Gene Deletion; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma
chemical_list: C497762:Notch1 protein, mouse; D051881:Receptor, Notch1