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ATDC mediates a TP63-regulated basal cancer invasive program

Phillip L Palmbos1,2, Yin Wang3,4, Armand Bankhead Iii4,5,6

  • 1Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA. ppalmbos@med.umich.edu.

Oncogene
|January 16, 2019
PubMed

Insights

The study reveals that the TP63 gene drives aggressive basal bladder cancers by activating the ATDC gene. ATDC is crucial for tumor invasion and metastasis, offering potential new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Basal subtype bladder cancers are aggressive, with poorly understood molecular drivers of lethality.
  • Ataxia-telangiectasia group D complementing gene (ATDC) promotes bladder tumor formation and invasion, but its regulation is unknown.
  • The aggressive basal subtype of bladder cancer is characterized by a TP63-driven gene program.

Purpose of the Study:

  • To investigate the relationship between TP63 and ATDC expression in basal bladder cancers.
  • To elucidate the role of TP63 in regulating ATDC and its contribution to aggressive tumor behavior.

Main Methods:

  • Analysis of ATDC expression in relation to TP63 and basal bladder cancer subtypes.
  • Chromatin immunoprecipitation assays to assess TP63 binding to ATDC and KRT14 regulatory regions.
  • In vivo studies to evaluate the requirement of ATDC in TP63-induced tumor invasion and metastasis.

Main Results:

  • ATDC expression is significantly linked with TP63 expression and is high in basal bladder cancers.
  • TP63 directly binds to the regulatory regions of ATDC and KRT14, enhancing their expression.
  • ATDC and KRT14 are essential components of the TP63-driven invasive program, with ATDC required for TP63-induced invasion and metastasis in vivo.

Conclusions:

  • TP63 activation drives an aggressive basal cancer program involving ATDC and KRT14.
  • ATDC is a key molecular determinant of aggressive basal bladder cancer behavior.
  • Targeting ATDC may offer novel therapeutic strategies and improved biomarkers for aggressive bladder cancers.

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