Abstract
The identification of functionally relevant subpopulations of therapy-resistant cancer cells is a challenge. These cells, intrinsically resistant to conventional therapy, can cause recurrence. Evidence has suggested that therapy-resistant cancer cells are likely epithelial–mesenchymal transition (EMT) cells and/or stem-like cells called cancer stem cells (CSCs). EMT, a normal embryological process that converts epithelial cells into mesenchymal cells, is frequently activated during cancer development and progression. CSCs are a small subpopulation of cancer cells within a tumor mass that have the ability to self-renew and maintain tumor-initiating capacity by giving rise to heterogeneous lineages of cancer cells that comprise the whole tumor. Although the origin of CSCs and EMT cells remains to be fully explored, a growing body of evidence has indicated that the biology of EMT and CSCs is strongly linked. Doublecortin-like kinase 1 (DCLK1), a cancer stem cell marker, is functionally involved in maintaining cancer stemness and the process of EMT important for cancer initiation, cancer metastasis, and secondary tumor formation. Therefore, targeting these cells may provide new strategies to overcome tumor heterogeneity, therapeutic resistance, and cancer relapse. In this review, we will provide a potential mechanistic link between EMT induction and the emergence of CSCs for the origin and progression of cancer. We will highlight the functional activity of DCLK1 in supporting EMT and cancer cell self-renewal, which will lead us to a better understanding of DCLK1 expression in cancer development and progression, and help us to develop targeted therapies for effective cancer treatment.
Highlights
Cancer mortality has steadily declined over the past decade, primarily due to earlier detection and adjuvant and targeted therapies, tumor recurrence remains a major cause of morbidity and mortality [1,2]
Chemo- or radio-resistant tumors are reported to have high numbers of epithelial–mesenchymal transition (EMT)-transformed cancer stem cells (CSCs) [3,7]. These findings suggest that EMT links CSCs, helping these cells to survive even in the peripheral circulation and actively causing relapse
Studies from us and others supported that Doublecortin-like kinase 1 (DCLK1) expression is critical for cancer growth, EMT, metastasis, and cancer cell self-renewal [9,14,16,17,18]
Summary
Cancer mortality has steadily declined over the past decade, primarily due to earlier detection and adjuvant and targeted therapies, tumor recurrence remains a major cause of morbidity and mortality [1,2]. This review will discuss the signaling mechanism linking EMT and CSCs, and discuss how the critical regulator Doublecortin-like kinase 1 (DCLK1) supports the EMT process and stemness for cancer development and progression. Studies from us and others supported that DCLK1 expression is critical for cancer growth, EMT, metastasis, and cancer cell self-renewal [9,14,16,17,18].
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