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CK1epsilon is required for breast cancers dependent on beta-catenin activity.

Publication ,  Journal Article
Kim, SY; Dunn, IF; Firestein, R; Gupta, P; Wardwell, L; Repich, K; Schinzel, AC; Wittner, B; Silver, SJ; Root, DE; Boehm, JS; Ramaswamy, S ...
Published in: PLoS One
February 1, 2010

BACKGROUND: Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date. METHODOLOGY: To uncover genetic dependencies in breast cancer cells that harbor active beta-catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized beta-catenin activity. Here we identify CSNK1E, the gene encoding casein kinase 1 epsilon (CK1epsilon) as required specifically for the proliferation of breast cancer cells with activated beta-catenin and confirm its role as a positive regulator of beta-catenin-driven transcription. Furthermore, we demonstrate that breast cancer cells that harbor activated beta-catenin activity exhibit enhanced sensitivity to pharmacological blockade of Wnt/beta-catenin signaling. We also find that expression of CK1epsilon is able to promote oncogenic transformation of human cells in a beta-catenin-dependent manner. CONCLUSIONS/SIGNIFICANCE: These studies identify CK1epsilon as a critical contributor to activated beta-catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active beta-catenin. More generally, these observations delineate an approach that can be used to identify druggable synthetic lethal interactions with signaling pathways that are frequently activated in cancer but are difficult to target with the currently available small molecule inhibitors.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

February 1, 2010

Volume

5

Issue

2

Start / End Page

e8979

Location

United States

Related Subject Headings

  • beta Catenin
  • Signal Transduction
  • RNA Interference
  • Phloroglucinol
  • Oligonucleotide Array Sequence Analysis
  • NIH 3T3 Cells
  • Mice
  • Indoles
  • Immunoblotting
  • Humans
 

Citation

APA
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MLA
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Kim, S. Y., Dunn, I. F., Firestein, R., Gupta, P., Wardwell, L., Repich, K., … Hahn, W. C. (2010). CK1epsilon is required for breast cancers dependent on beta-catenin activity. PLoS One, 5(2), e8979. https://doi.org/10.1371/journal.pone.0008979
Kim, So Young, Ian F. Dunn, Ron Firestein, Piyush Gupta, Leslie Wardwell, Kara Repich, Anna C. Schinzel, et al. “CK1epsilon is required for breast cancers dependent on beta-catenin activity.PLoS One 5, no. 2 (February 1, 2010): e8979. https://doi.org/10.1371/journal.pone.0008979.
Kim SY, Dunn IF, Firestein R, Gupta P, Wardwell L, Repich K, et al. CK1epsilon is required for breast cancers dependent on beta-catenin activity. PLoS One. 2010 Feb 1;5(2):e8979.
Kim, So Young, et al. “CK1epsilon is required for breast cancers dependent on beta-catenin activity.PLoS One, vol. 5, no. 2, Feb. 2010, p. e8979. Pubmed, doi:10.1371/journal.pone.0008979.
Kim SY, Dunn IF, Firestein R, Gupta P, Wardwell L, Repich K, Schinzel AC, Wittner B, Silver SJ, Root DE, Boehm JS, Ramaswamy S, Lander ES, Hahn WC. CK1epsilon is required for breast cancers dependent on beta-catenin activity. PLoS One. 2010 Feb 1;5(2):e8979.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

February 1, 2010

Volume

5

Issue

2

Start / End Page

e8979

Location

United States

Related Subject Headings

  • beta Catenin
  • Signal Transduction
  • RNA Interference
  • Phloroglucinol
  • Oligonucleotide Array Sequence Analysis
  • NIH 3T3 Cells
  • Mice
  • Indoles
  • Immunoblotting
  • Humans