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Disease-associated casein kinase I delta mutation may promote adenomatous polyps formation via a Wnt/beta-catenin independent mechanism.

Publication ,  Journal Article
Tsai, I-C; Woolf, M; Neklason, DW; Branford, WW; Yost, HJ; Burt, RW; Virshup, DM
Published in: Int J Cancer
March 1, 2007

The Wnt signaling pathway is critical for embryonic development and is dysregulated in multiple cancers. Two closely related isoforms of casein kinase I (CKIdelta and epsilon) are positive regulators of this pathway. We speculated that mutations in the autoinhibitory domain of CKIdelta/epsilon might upregulate CKIdelta/epsilon activity and hence Wnt signaling and increase the risk of adenomatous polyps and colon cancer. Exons encoding the CKIepsilon and CKIdelta regulatory domains were sequenced from DNA obtained from individuals with adenomatous polyps and a family history of colon cancer unaffected by familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer (HNPCC). A CKIdelta missense mutation, changing a highly conserved residue, Arg324, to His (R324H), was found in an individual with large and multiple polyps diagnosed at a relatively young age. Two findings indicate that this mutation is biologically active. First, ectopic ventral expression of CKIdelta(R324H) in Xenopus embryos results in secondary axis formation with an additional distinctive phenotype (altered morphological movements) similar to that seen with unregulated CKIepsilon. Second, CKIdelta(R324H) is more potent than wildtype CKIdelta in transformation of RKO colon cancer cells. Although the R324H mutation does not significantly change CKIdelta kinase activity in an in vitro kinase assay or Wnt/beta-catenin signal transduction as assessed by a beta-catenin reporter assay, it alters morphogenetic movements via a beta-catenin-independent mechanism in early Xenopus development. This novel human CKIdelta mutation may alter the physiological role and enhance the transforming ability of CKIdelta through a Wnt/beta-catenin independent mechanism and thereby influence colonic adenoma development.

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Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

March 1, 2007

Volume

120

Issue

5

Start / End Page

1005 / 1012

Location

United States

Related Subject Headings

  • beta Catenin
  • Xenopus
  • Wnt Proteins
  • Pedigree
  • Oncology & Carcinogenesis
  • Mutation
  • Molecular Sequence Data
  • Humans
  • Histidine
  • Heterozygote
 

Citation

APA
Chicago
ICMJE
MLA
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Tsai, I.-C., Woolf, M., Neklason, D. W., Branford, W. W., Yost, H. J., Burt, R. W., & Virshup, D. M. (2007). Disease-associated casein kinase I delta mutation may promote adenomatous polyps formation via a Wnt/beta-catenin independent mechanism. Int J Cancer, 120(5), 1005–1012. https://doi.org/10.1002/ijc.22368
Tsai, I-Chun, Margaret Woolf, Deborah W. Neklason, William W. Branford, H Joseph Yost, Randall W. Burt, and David M. Virshup. “Disease-associated casein kinase I delta mutation may promote adenomatous polyps formation via a Wnt/beta-catenin independent mechanism.Int J Cancer 120, no. 5 (March 1, 2007): 1005–12. https://doi.org/10.1002/ijc.22368.
Tsai I-C, Woolf M, Neklason DW, Branford WW, Yost HJ, Burt RW, et al. Disease-associated casein kinase I delta mutation may promote adenomatous polyps formation via a Wnt/beta-catenin independent mechanism. Int J Cancer. 2007 Mar 1;120(5):1005–12.
Tsai, I. Chun, et al. “Disease-associated casein kinase I delta mutation may promote adenomatous polyps formation via a Wnt/beta-catenin independent mechanism.Int J Cancer, vol. 120, no. 5, Mar. 2007, pp. 1005–12. Pubmed, doi:10.1002/ijc.22368.
Tsai I-C, Woolf M, Neklason DW, Branford WW, Yost HJ, Burt RW, Virshup DM. Disease-associated casein kinase I delta mutation may promote adenomatous polyps formation via a Wnt/beta-catenin independent mechanism. Int J Cancer. 2007 Mar 1;120(5):1005–1012.
Journal cover image

Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

March 1, 2007

Volume

120

Issue

5

Start / End Page

1005 / 1012

Location

United States

Related Subject Headings

  • beta Catenin
  • Xenopus
  • Wnt Proteins
  • Pedigree
  • Oncology & Carcinogenesis
  • Mutation
  • Molecular Sequence Data
  • Humans
  • Histidine
  • Heterozygote