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Sorcin promotes migration in cancer and regulates the EGF-dependent EGFR signaling pathways.
Tito, Claudia; Genovese, Ilaria; Giamogante, Flavia; Benedetti, Anna; Miglietta, Selenia; Barazzuol, Lucia; Cristiano, Loredana; Iaiza, Alessia; Carolini, Sabatino; De Angelis, Luciana; Masciarelli, Silvia; Nottola, Stefania Annarita; Familiari, Giuseppe; Petrozza, Vincenzo; Lauriola, Mattia; Tamagnone, Luca; Ilari, Andrea; Calì, Tito; Valdivia, Hector H; Valdivia, Carmen R; Colotti, Gianni; Fazi, Francesco.
Affiliation
  • Tito C; Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy.
  • Genovese I; Institute of Molecular Biology and Pathology, Italian National Research Council, IBPM-CNR, P.le A. Moro 5, 00185, Rome, Italy.
  • Giamogante F; Department of Biomedical Sciences, University of Padova, Padua, Italy.
  • Benedetti A; Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy.
  • Miglietta S; Section of Human Anatomy, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
  • Barazzuol L; Department of Biomedical Sciences, University of Padova, Padua, Italy.
  • Cristiano L; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
  • Iaiza A; Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy.
  • Carolini S; Institute of Molecular Biology and Pathology, Italian National Research Council, IBPM-CNR, P.le A. Moro 5, 00185, Rome, Italy.
  • De Angelis L; Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy.
  • Masciarelli S; Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy.
  • Nottola SA; Section of Human Anatomy, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
  • Familiari G; Section of Human Anatomy, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
  • Petrozza V; Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
  • Lauriola M; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
  • Tamagnone L; Department of Life Science and Public Health, Histology and Embryology Unit - Catholic University of the Sacred Hearth, Fondazione Policlinico Gemelli - IRCCS, Rome, Italy.
  • Ilari A; Institute of Molecular Biology and Pathology, Italian National Research Council, IBPM-CNR, P.le A. Moro 5, 00185, Rome, Italy.
  • Calì T; Department of Biomedical Sciences, University of Padova, Padua, Italy.
  • Valdivia HH; Department of Medicine, Cardiovascular Research Center, University of Wisconsin, Madison, WI, USA.
  • Valdivia CR; Department of Medicine, Cardiovascular Research Center, University of Wisconsin, Madison, WI, USA.
  • Colotti G; Institute of Molecular Biology and Pathology, Italian National Research Council, IBPM-CNR, P.le A. Moro 5, 00185, Rome, Italy.
  • Fazi F; Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy. francesco.fazi@uniroma1.it.
Cell Mol Life Sci ; 80(8): 202, 2023 Jul 13.
Article in En | MEDLINE | ID: mdl-37442828
ABSTRACT
The epidermal growth factor receptor (EGFR) is one of the main tumor drivers and is an important therapeutic target for many cancers. Calcium is important in EGFR signaling pathways. Sorcin is one of the most important calcium sensor proteins, overexpressed in many tumors, that promotes cell proliferation, migration, invasion, epithelial-to-mesenchymal transition, malignant progression and resistance to chemotherapeutic drugs. The present work elucidates a functional mechanism that links calcium homeostasis to EGFR signaling in cancer. Sorcin and EGFR expression are significantly correlated and associated with reduced overall survival in cancer patients. Mechanistically, Sorcin directly binds EGFR protein in a calcium-dependent fashion and regulates calcium (dys)homeostasis linked to EGF-dependent EGFR signaling. Moreover, Sorcin controls EGFR proteostasis and signaling and increases its phosphorylation, leading to increased EGF-dependent migration and invasion. Of note, silencing of Sorcin cooperates with EGFR inhibitors in the regulation of migration, highlighting calcium signaling pathway as an exploitable target to enhance the effectiveness of EGFR-targeting therapies.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Epidermal Growth Factor / Neoplasms Limits: Humans Language: En Journal: Cell Mol Life Sci Year: 2023 Document type: Article
Fulltext
Print
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Epidermal Growth Factor / Neoplasms Limits: Humans Language: En Journal: Cell Mol Life Sci Year: 2023 Document type: Article