Su1995 Short (S) Isoform of Cancer-Stem-Cell Marker, DCLK1, Is Critically Required for Maintaining Proliferative/Tumorigenic Potential of Human Colon Cancer Cells (hCCCs) Independent of DCLK1-L Isoform

A novel antibody against cancer stem cell biomarker, DCLK1-S, is potentially useful for assessing colon cancer risk after screening colonoscopy

“…Absence of the microtubule binding domain in the S isoform, may allow differential localization of the two proteins, as suggested by the EM results ( Fig 5b ). Differences in localization of the S/L isoforms may lend itself to differences in the biological activity of the two isoforms as recently reported by us in a preliminary study ( 38 ). Colon cancer cells over-expressing the S isoform (COLO205-S-GFP) were found to be significantly more invasive, in vitro and in vivo , compared to the isogenic cells over-expressing the L-isoform (COLO205-L-GFP) ( 38 ).…”

“…Even though the short isoform is >98% homologous with the C-terminal end of the long isoform ( 12 ), the S-isoform lacks the double-cortin domains which is required for binding microtubules ( 36 , 37 ). In preliminary studies, we recently reported that colon cancer cells overexpressing the S-isoform were significantly more invasive than isogenic cells overexpressing the L-isoform ( 38 ). We therefore hypothesized that the sub-cellular localization of the S-isoform may be different from that of the L-isoform, and examined localization of the two isoforms by electron microscopy (EM) of isogenic colon cancer cells which overexpressed GFP tagged L- (COLO205-L-GFP) or S-isoform (COLO205-S-GFP); control clones expressed GFP from the control vector (COLO205-C).…”

FOXD3 Regulates CSC Marker, DCLK1-S, and Invasive Potential: Prognostic Implications in Colon Cancer

“…In preliminary studies, we reported that DCLK1-S overex-pression in hCCCs imparts a potent invasive potential to the cells (47), which was confirmed in here (Fig. 7C).…”

Epigenetic regulation of human DCLK-1 gene during colon-carcinogenesis: clinical and mechanistic implications

“…However, it is also true that in mouse models of colon carcinogenesis, metastatic lesions to the liver or lung have not been reported. It is therefore speculated that lack of expression of DCLK1-S by mouse tumors, may render the tumors non-invasive/ non-metastatic, unlike hCRCs, based on the results of our preliminary findings (46). There may thus be significant differences in the biology of epithelial tumors expressing long ± short isoforms of DCLK1, which needs to be further explored.…”

“…The crystal structure of the full-length isoforms 1 and 2 remains unknown to-date, even though the crystal structure of specific domains has been published, as described above. In a preliminary study we recently reported that the biological activity of DCLK1-S (isoform 2) was significantly different from that of DCLK1-L (isoform 1) (46); hCCCs expressing DCLK1-S developed an invasive phenotype while hCCCs expressing neither or overexpressing isoform 1 alone, lacked invasive and metastatic potential (46). It is therefore speculated that human epithelial cancers, including hCRCs, positive for DCLK1-S expressing CSCs, will form metastatic lesions within shorter intervals, compared to cancerous tumors negative for DCLK1-S expressing CSCs.…”