DCLK1-B depletion impairs cancer stemness resulting in reduced survival potential and increased apoptosis, thus sensitizing colorectal cancer to chemoradiation.
Collectively, our findings identify DCLK1 as a pivotal regulator of an EMT axis in CRC, thus implicating DCLK1 as a potential therapeutic target for CRC metastasis.
Human colorectal tumors (CRCs) and hCCCs express a novel short isoform of DCLK1 (DCLK1-S; isoform 2) from β-promoter of hDCLK1 gene, while normal colons express long isoform (DCLK1-L; isoform 1) from 5'(α)-promoter, suggesting that DCLK1-S, and not DCLK1-L, marks cancer stem cells (CSCs).
Finally, compared to normal colon biopsies and hyperplastic polyps, DCLK1 expression increased in human tubular adenomas and invasive colorectal cancers.
Double cortin-like kinase 1 (DCLK1) is a promising therapeutic target and cancer stem cell marker, predominantly investigated in pancreatic and colorectal cancer.
Moreover, the higher expression level of DCLK1 in patients undergoing CRT can propose it as a more relevant candidate among CSC markers comparing to Lgr5 for CRC patients.
In a recent study, we identified frequently methylated genes for cholangiocarcinoma (CDO1, DCLK1, SFRP1 and ZSCAN18), where one of these genes, DCLK1, was also confirmed to be highly methylated in colorectal cancer.
We further showed by Affymetrix exon arrays that DCLK1 is significantly downregulated in human colorectal cancer (n = 125) compared with normal colonic mucosa (n = 15), which was further confirmed by real-time RT-PCR of a subgroup of the samples.
Expression of DCAMKL-1 was increased in human colorectal cancers. siRNA-mediated blockade of DCAMKL-1 resulted in H tumor xenograft growth arrest, increased pri-let-7a miRNA, a corresponding decrease in luciferase activity, and decreased expression of the oncogene c-Myc.