Stefania Tocci1, Stella-Rita Ibeawuchi1, Soumita Das2, Ibrahim M Sayed3,4. 1. Department of Pathology, University of California San Diego, La Jolla, CA, USA. 2. Department of Pathology, University of California San Diego, La Jolla, CA, USA. sodas@health.ucsd.edu. 3. Department of Pathology, University of California San Diego, La Jolla, CA, USA. i4ibrahim@health.ucsd.edu. 4. Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt. i4ibrahim@health.ucsd.edu.
Abstract
BACKGROUND: Engulfment and cell motility protein 1 (ELMO1) is a key protein for innate immunity since it is required for the clearance of apoptotic cells and pathogenic bacteria as well as for the control of inflammatory responses. ELMO1, through binding with Dock180 and activation of the Rac1 signaling pathway, plays a significant role in cellular shaping and motility. Rac-mediated actin cytoskeletal rearrangement is essential for bacterial phagocytosis, but also plays a crucial role in processes such as cancer cell invasion and metastasis. While the role of ELMO1 in bacterial infection and inflammatory responses is well established, its implication in cancer is not widely explored yet. Molecular changes or epigenetic alterations such as DNA methylation, which ultimately leads to alterations in gene expression and deregulation of cellular signaling, has been reported for ELMO1 in different cancer types. CONCLUSIONS: In this review, we provide an updated and comprehensive summary of the roles of ELMO1 in infection, inflammatory diseases and cancer. We highlight the possible mechanisms regulated by ELMO1 that are relevant for cancer development and progression and provide insight into the possible use of ELMO1 as a diagnostic biomarker and therapeutic target.
BACKGROUND: Engulfment and cell motility protein 1 (ELMO1) is a key protein for innate immunity since it is required for the clearance of apoptotic cells and pathogenic bacteria as well as for the control of inflammatory responses. ELMO1, through binding with Dock180 and activation of the Rac1 signaling pathway, plays a significant role in cellular shaping and motility. Rac-mediated actin cytoskeletal rearrangement is essential for bacterial phagocytosis, but also plays a crucial role in processes such as cancer cell invasion and metastasis. While the role of ELMO1 in bacterial infection and inflammatory responses is well established, its implication in cancer is not widely explored yet. Molecular changes or epigenetic alterations such as DNA methylation, which ultimately leads to alterations in gene expression and deregulation of cellular signaling, has been reported for ELMO1 in different cancer types. CONCLUSIONS: In this review, we provide an updated and comprehensive summary of the roles of ELMO1 in infection, inflammatory diseases and cancer. We highlight the possible mechanisms regulated by ELMO1 that are relevant for cancer development and progression and provide insight into the possible use of ELMO1 as a diagnostic biomarker and therapeutic target.
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