title: CD147: regulator of hyaluronan signaling in invasiveness and chemoresistance.
abstract: Major determinants that influence negative outcome in cancer patients are the abilities of cancer cells to resist current therapies and to invade surrounding host tissue, consequently leading to local and metastatic dissemination. Hyaluronan (HA), a prominent constituent of the tumor microenvironment, not only provides structural support but also interacts with cell surface receptors, especially CD44, that influence cooperative signaling pathways leading to chemoresistance and invasiveness. CD147 (emmprin; basigin) is a member of the Ig superfamily that has also been strongly implicated in chemoresistance and invasiveness. CD147 both regulates HA synthesis and interacts with the HA receptors, CD44, and LYVE-1. Increased CD147 expression induces formation of multiprotein complexes containing CD44 (or LYVE-1) as well as members of the membrane-type matrix metalloproteinase, receptor tyrosine kinase, ABC drug transporter, or monocarboxylate transporter families, which become assembled in specialized lipid raft domains along with CD147 itself. In each case, multivalent HA-receptor interactions are essential for formation or stabilization of the lipid raft complexes and for downstream signaling pathways or transporter activities that are driven by these complexes. We conclude that cooperativity between HA, HA receptors, and CD147 may be a major driver of the interconnected pathways of invasiveness and chemoresistance widely critical to malignancy.
authors: Department of Regenerative Medicine & Cell Biology, Medical University of South Carolina, Charleston, South Carolina, USA. Electronic address: grass@musc.edu.
authors: G Daniel
authors: GD
authors: Grass
authors: Department of Medicine, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors: Lu
authors: L
authors: Dai
authors: Department of Microbiology, Immunology & Parasitology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors: Zhiqiang
authors: Z
authors: Qin
authors: Department of Medicine, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA; Department of Microbiology, Immunology & Parasitology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors: Chris
authors: C
authors: Parsons
authors: Department of Regenerative Medicine & Cell Biology, Medical University of South Carolina, Charleston, South Carolina, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA. Electronic address: toolebp@musc.edu.
authors: Bryan P
authors: BP
authors: Toole
mesh_terms: D000818:Animals; D051926:Basigin / Q000378:metabolism*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006564:Herpesviridae / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D021962:Membrane Microdomains; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011485:Protein Binding; D012514:Sarcoma, Kaposi / Q000378:metabolism; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C497886:BSG protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C119248:LYVE1 protein, human; D027501:Monocarboxylic Acid Transporters; D033921:Vesicular Transport Proteins; D051926:Basigin; D006820:Hyaluronic Acid
keywords: ABC drug transporters; CD147; CD44; Chemoresistance; Hyaluronan; Invasiveness; LYVE-1; Lipid rafts; Monocarboxylate transporters; Receptor tyrosine kinases