TY - JOUR
T1 - Role of CD44 isoforms in epithelial-mesenchymal plasticity and metastasis
AU - Primeaux, Mark
AU - Gowrikumar, Saiprasad
AU - Dhawan, Punita
N1 - Funding Information:
This study was supported by BX002086 (VA merit), CA250383 (NIH/NCI), CA216746 (NIH/NCI) and Nebraska Research Initiative (NRI) to P.D.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature B.V.
PY - 2022/6
Y1 - 2022/6
N2 - Cellular plasticity lies at the core of cancer progression, metastasis, and resistance to treatment. Stemness and epithelial-mesenchymal plasticity in cancer are concepts that represent a cancer cell’s ability to coopt and adapt normal developmental programs to promote survival and expansion. The cancer stem cell model states that a small subset of cancer cells with stem cell-like properties are responsible for driving tumorigenesis and metastasis while remaining especially resistant to common chemotherapeutic drugs. Epithelial-mesenchymal plasticity describes a cancer cell’s ability to transition between epithelial and mesenchymal phenotypes which drives invasion and metastasis. Recent research supports the existence of stable epithelial/mesenchymal hybrid phenotypes which represent highly plastic states with cancer stem cell characteristics. The cell adhesion molecule CD44 is a widely accepted marker for cancer stem cells, and it lies at a functional intersection between signaling networks regulating both stemness and epithelial-mesenchymal plasticity. CD44 expression is complex, with alternative splicing producing many isoforms. Interestingly, not only does the pattern of isoform expression change during transitions between epithelial and mesenchymal phenotypes in cancer, but these isoforms have distinct effects on cell behavior including the promotion of metastasis and stemness. The role of CD44 both downstream and upstream of signaling pathways regulating epithelial-mesenchymal plasticity and stemness make this protein a valuable target for further research and therapeutic intervention.
AB - Cellular plasticity lies at the core of cancer progression, metastasis, and resistance to treatment. Stemness and epithelial-mesenchymal plasticity in cancer are concepts that represent a cancer cell’s ability to coopt and adapt normal developmental programs to promote survival and expansion. The cancer stem cell model states that a small subset of cancer cells with stem cell-like properties are responsible for driving tumorigenesis and metastasis while remaining especially resistant to common chemotherapeutic drugs. Epithelial-mesenchymal plasticity describes a cancer cell’s ability to transition between epithelial and mesenchymal phenotypes which drives invasion and metastasis. Recent research supports the existence of stable epithelial/mesenchymal hybrid phenotypes which represent highly plastic states with cancer stem cell characteristics. The cell adhesion molecule CD44 is a widely accepted marker for cancer stem cells, and it lies at a functional intersection between signaling networks regulating both stemness and epithelial-mesenchymal plasticity. CD44 expression is complex, with alternative splicing producing many isoforms. Interestingly, not only does the pattern of isoform expression change during transitions between epithelial and mesenchymal phenotypes in cancer, but these isoforms have distinct effects on cell behavior including the promotion of metastasis and stemness. The role of CD44 both downstream and upstream of signaling pathways regulating epithelial-mesenchymal plasticity and stemness make this protein a valuable target for further research and therapeutic intervention.
KW - CD44 isoforms
KW - Cancer stem cells
KW - Epithelial-mesenchymal plasticity
KW - Metastasis
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U2 - 10.1007/s10585-022-10146-x
DO - 10.1007/s10585-022-10146-x
M3 - Review article
C2 - 35023031
AN - SCOPUS:85122788132
VL - 39
SP - 391
EP - 406
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
SN - 0262-0898
IS - 3
ER -