title: Osteopontin-A Master Regulator of Epithelial-Mesenchymal Transition.
abstract: Osteopontin (OPN) plays an important functional role in both physiologic and pathologic states. OPN is implicated in the progression of fibrosis, cancer, and metastatic disease in several organ systems. The epithelial-mesenchymal transition (EMT), first described in embryology, is increasingly being recognized as a significant contributor to fibrotic phenotypes and tumor progression. Several well-established transcription factors regulate EMT and are conserved across tissue types and organ systems, including TWIST, zinc finger E-box-binding homeobox (ZEB), and SNAIL-family members. Recent literature points to an important relationship between OPN and EMT, implicating OPN as a key regulatory component of EMT programs. In this review, OPN's interplay with traditional EMT activators, both directly and indirectly, will be discussed. Also, OPN's ability to restructure the tissue and tumor microenvironment to indirectly modify EMT will be reviewed. Together, these diverse pathways demonstrate that OPN is able to modulate EMT and provide new targets for directing therapeutics.
authors.affiliation: Loyola University Medical Center, Department of Surgery, 2160 S First Ave, Maywood, IL 60153, USA. ankothari@lumc.edu.|Burn and Shock Trauma Institute, Loyola University Chicago, 2160 S First Ave, Maywood, IL 60153, USA. ankothari@lumc.edu.
authors.forename: Anai N
authors.initials: AN
authors.lastname: Kothari
authors.affiliation: Loyola University Medical Center, Department of Surgery, 2160 S First Ave, Maywood, IL 60153, USA. marffa@luc.edu.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Arffa
authors.affiliation: Loyola University Medical Center, Department of Surgery, 2160 S First Ave, Maywood, IL 60153, USA. vchang@luc.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Chang
authors.affiliation: Loyola University Medical Center, Department of Surgery, 2160 S First Ave, Maywood, IL 60153, USA. rblackwell@lumc.edu.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Blackwell
authors.affiliation: Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA. synw@musc.edu.
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Syn
authors.affiliation: The Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA. jzhang@luc.edu.
authors.forename: Jiwang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Loyola University Medical Center, Department of Surgery, 2160 S First Ave, Maywood, IL 60153, USA. zhmi@luc.edu.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Mi
authors.affiliation: Loyola University Medical Center, Department of Surgery, 2160 S First Ave, Maywood, IL 60153, USA. paul.kuo@luhs.org.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Kuo
keywords: cancer-associated fibroblasts; epithelial-mesenchymal transition; fibrosis; osteopontin; tumor metastasis; tumor microenvironment