Epigenetic regulation of human DCLK-1 gene during coloncarcinogenesis: Clinical and mechanistic implications

Pomila Singh, Malaney O'Connell, Sarkar Shubhashish

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations


Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with a family history (genetic predisposition), ~75% of CRCs are due to age-associated accumulation of epigenetic alterations which can result in the suppression of key tumor suppressor genes leading to mutations and activation of oncogenic pathways. Sporadic colon-carcinogenesis is facilitated by many molecular pathways of genomic instability which include chromosomal instability (CIN), micro-satellite instability (MSI) and CpG island methylator phenotype (CIMP), leading towards loss of homeostasis and onset of neoplastic transformation. The unopposed activation of Wnt/ß-catenin pathways, either due to loss of APC function or up-regulation of related stimulatory pathways, results in unopposed hyperproliferation of colonic crypts, considered the single most important risk factor for colon carcinogenesis. Hypermethylation of CpG islands within the promoters of specific genes can potentially inactivate DNA repair genes and/or critical tumor suppressor genes. Recently, CpG methylation of the 5' promoter of human (h) DCLK1 gene was reported in many human epithelial cancers, including colorectal cancers (CRCs), resulting in the loss of expression of the canonical long isoform of DCLK1 (DCLK1-L) in hCRCs. Instead, a shorter isoform of DCLK1 (DCLK1-S) was discovered to be expressed in hCRCs, from an alternate ß promoter of DCLKL1-gene; the clinical and biological implications of these novel findings, in relation to recent publications is discussed.

Original languageEnglish (US)
Article number51
JournalStem Cell Investigation
Issue numberSEP
StatePublished - Sep 1 2016
Externally publishedYes


  • 5'(a) and IntronV(ß) promoters of hDCLK1-gene
  • Cancer stem cells (CSCs)
  • Colorectal cancers (CRCs)
  • DCLK1-long isoform (DCLK1-L)
  • Short isoform of DCLK1 (DCLK1-S)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Cell Biology


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