Study on Molecular Biological Function of DCLK1B in Colorectal Cancer

Abstract

Aberrant overactivation of Wnt signaling has been observed in multiple cancer types such as melanoma, breast cancer, and colorectal cancer (CRC). Cancer stem cells (CSCs) are major reason of metastasis and recurrence inducing high mortality in CRC patients due to their self-renewal ability and diverse differentiation potential. In this CSCs populations, the abnormal activation of Wnt signaling occurs. Overactivation of Wnt signaling increases the stemness in CSCs by increasing their self-renewal and survival potential. Therefore, the regulation of CSC function by targeting Wnt signaling is important in cancer therapy. Doublecortin-like kinase 1 (DCLK1), a downstream target of Wnt signaling, stimulates cancer cell proliferation, survival, drug-resistance, and metastasis inducing CRC malignancy. In addition, DCLK1 is a well-known oncogene comprised of the A and B isoform. DCLK1B is the principal form in colorectal cancer, but, its role in colorectal cancer malignancy has not been well characterized. In this study, role of DCLK1B in colorectal cancer malignancy was investigated by developing multiple cell lines. DCLK1B overexpressing and knock-out cells were developed using the human CRC cell line such as HCT116. DCLK1B transient knock-down cells were developed using CRC cell line and patient-derived CRC cell lines. The current data identified that DCLK1B stimulates cell proliferation and increases anti-apoptotic function, survival ability, and metastatic potential. The results of this study provide the crucial framework for the treatment of CRC.