title: Hyaluronan-CD44 interaction promotes oncogenic signaling, microRNA functions, chemoresistance, and radiation resistance in cancer stem cells leading to tumor progression.
abstract: Hyaluronan (HA), a major component of the extracellular matrix (ECM), is enriched in many types of tumors. There is good evidence linking high levels of HA production in human carcinomas to an aggressive phenotype and tumor metastasis. HA is generally bound to CD44 isoforms (so-called CD44s and CD44v3) which are ubiquitous, abundant, and functionally important cell surface receptors. This chapter describes the evidence for HA/CD44v3-mediated activation of the cytoskeleton (e.g., ankyrin and GTPases) and matrix metalloproteinase (MMP) signaling during tumor progression. A special focus is placed on the role of HA-CD44v3 interaction in cancer stem cells (CSCs). Matrix HA is known to be present in CSC niches. Since CD44v3 serves as a CSC marker, it provides an important physical linkage between matrix HA and various transcription factors that regulate tumor cell functions through distinct signaling pathways. CSCs are known to be chemoresistant and/or radiation resistant and to cause cancer relapse. The purpose of this chapter is to review the most current research on the cellular and molecular biology of CSCs. The emphasis will be placed on both CSC niche and matrix HA-induced microRNA signaling plus various CSC functions (e.g., self-renewal, differentiation, and chemoresistance) during cancer progression. Understanding the regulation of CSCs is critically important for designing CSC-specific therapeutic targets to prevent cancer development and progression.
authors: Department of Medicine, University of California at San Francisco & Endocrine Unit (111N), VA Medical Center, San Francisco, California, USA. Electronic address: lilly.bourguignon@ucsf.edu.
authors: Lilly Y W
authors: LY
authors: Bourguignon
authors: Department of Medicine, University of California at San Francisco & Endocrine Unit (111N), VA Medical Center, San Francisco, California, USA.
authors: Marisa
authors: M
authors: Shiina
authors: Department of Radiation Oncology, University of California Davis, Sacramento, California, USA.
authors: Jian-Jian
authors: JJ
authors: Li
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000737:chemistry; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D003599:Cytoskeleton / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000737:chemistry
chemical_list: D017487:Ankyrins; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D035683:MicroRNAs; D006820:Hyaluronic Acid; D020741:rho GTP-Binding Proteins
keywords: CD44; Cancer stem cells; Chemoresistance; Matrix hyaluronan; Radiation resistance; Tumor progression; microRNAs