The role of CD44 in epithelial–mesenchymal transition and cancer development

Abstract

CD44, a multi-structural and multifunctional transmembrane glycoprotein, was initially identified as a receptor for hyaluronan that participates in both physiological and pathological processes. CD44 is found to be closely linked to the development of various solid tumors. Molecular studies have revealed that high CD44 expression was correlated with the phenotypes of cancer stem cells and epithelial–mesenchymal transition, thereby contributing to tumor invasion, metastasis, recurrence, and chemoresistance. Correspondingly, blockade of CD44 has been demonstrated to be capable of attenuating the malignant phenotype, slowing cancer progression, and reversing therapy resistance. Clinical analyses showed that high CD44 expression is associated with poor survival of various cancer patients, indicating that CD44 can be a potential prognostic marker. In this review, we summarize recent research progress of CD44 on tumor biology and the clinical significance of CD44.

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

“…Finally, CD44 associates with EMT-related transcription factors, e.g., the Wnt signaling pathway via CD44-associated LRP6 (LDL receptor related protein6) (Xu et al, 2015). Of central importance for the engagement of CD44 as a CIC marker are the associations with non-RTK (Cooper and Qian, 2008; Nastase et al, 2017), which can proceed via activated RTK, GPCR, cytoskeletal linker proteins, or directly via GEM-recruited CD44v (Ingley, 2008; Ekyalongo et al, 2015; Korcsmaros et al, 2017).…”

Associations of five polymorphisms in the CD44 gene with cancer susceptibility in Asians

“…The full-length CD44 gene is located on chromosome 11 and consists of 20 exons and 19 introns15. Transcripts for the CD44 gene undergo complicated alternative splicing, which results in many functionally distinct protein isoforms, such as CD44 standard (CD44s) and CD44 variant isoforms (CD44v), which account for the heterogeneity in this protein family145.…”

“…Transcripts for the CD44 gene undergo complicated alternative splicing, which results in many functionally distinct protein isoforms, such as CD44 standard (CD44s) and CD44 variant isoforms (CD44v), which account for the heterogeneity in this protein family145. It is widely accepted that CD44 is expressed as multiple transcriptional variants, but the 3′UTR, which is ~3000 nucleotides long, is in fact relatively conserved214.…”

“…First, CD44 is found to be widely expressed in various cancers, and its expression correlates with poor prognosis1345. In functional studies, specific targeted knockdown of CD44 has been shown to impede cancer progression6.…”

Editorial: Interaction Between Hyaluronic Acid and Its Receptors (CD44, RHAMM) Regulates the Activity of Inflammation and Cancer

“…Standard CD44 is the smallest and most abundant isoform, whereas the other variants are expressed in a cell-specific manner (e.g., on epithelial cells or keratinocytes), as well as in multiple pathologies, including rheumatoid arthritis, diabetes, multiple sclerosis, and cancer (2, 6). The physiological activities of CD44 stem from its multiple functions, including mediating cell–cell and cell–matrix interactions, cell proliferation, cell adhesion, cell migration, hematopoiesis, lymphocyte activation, cell homing, cell extravasation, cell survival, and apoptosis, as well as epithelial–mesenchymal transition (EMT) (7). However, these functions can be converted to pathological activities when exaggerated or they escape out of control, like in cancer or chronic inflammation.…”