Hyaluronan-CD44 interaction promotes microRNA signaling and RhoGTPase activation leading to tumor progression
Open Access
- 1 January 2012
- journal article
- comment
- Published by Taylor & Francis Ltd in Small GTPases
- Vol. 3 (1), 53-59
- https://doi.org/10.4161/sgtp.19110
Abstract
A hallmark of all solid tumor malignancies is the ability to invade the surrounding tissue and/or metastasize to distant sites. Tumors cells have altered signaling pathways which that to cytoskeleton activation and migration. Myriad studies have attempted to identify specific adhesion molecule(s) expressed in solid tumor cells that correlate with tumor cell migrative and invasive behaviors. Among such candidate molecules is hyaluronan (HA), the major glycosaminoglycan component of extracellular matrix (ECM). HA serves not only as a primary constituent of connective tissue extracellular matrices but also functions as a bio-regulatory molecule. Pertinently, HA is enriched in many types of tumors. HA is capable of binding to CD44 which is a ubiquitous, abundant and functionally important receptor expressed on the surface of many normal cells and tumor cells. Several lines of evidence indicate that CD44 selects its unique downstream effectors and coordinates downstream, intracellular signaling pathways that influence multiple cellular functions. Certain microRNAs [(miRNAs), small RNA molecules with ~20–25 nucleotides] have been shown to play roles in regulating tumor cell migration, invasion, survival and chemotherapy resistance. In this article, a special focus is placed on the role of HA-mediated CD44 interaction with unique signaling molecules in activating intracellular miRNA-signaling and RhoGTPase functions leading to the concomitant onset of tumor cell activities (e.g., tumor cell migration, invasion, survival and chemoresistance) and tumor progression. This new knowledge could serve as groundwork for the future development of new drug targets to inhibit HA/CD44-mediated oncogenic signaling and cancer progression.Keywords
This publication has 30 references indexed in Scilit:
- Role of Hyaluronan-Mediated CD44 Signaling in Head and Neck Squamous Cell Carcinoma Progression and ChemoresistanceThe American Journal of Pathology, 2011
- Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progressionSeminars in Cancer Biology, 2008
- Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions?Journal of Cell Science, 2008
- Hyaluronidases: Their Genomics, Structures, and Mechanisms of ActionChemical Reviews, 2006
- Tumor cell invasion and survival in head and neck cancerCancer and Metastasis Reviews, 2005
- Distant metastasis in breast cancer: molecular mechanisms and therapeutic targets.Cancer Biology & Therapy, 2003
- Hyaluronan-Cell Interactions in Cancer and Vascular DiseaseOnline Journal of Public Health Informatics, 2002
- LYVE-1, the lymphatic system and tumor lymphangiogenesisTrends in Immunology, 2001
- Hyaluronan: a multifunctional, megaDalton, stealth moleculeCurrent Opinion in Cell Biology, 2000
- Rho GTPases and the Actin CytoskeletonScience, 1998