ATMIN enhances invasion by altering PARP1 in MSS colorectal cancer

Yue-Ju Li1,2, Cheng-Ning Yang1, Mark Yen-Ping Kuo1

  • 1Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University Taipei, Taiwan.

Insights

Ataxia-telangiectasia mutated interactor (ATMIN) promotes colorectal cancer (CRC) progression in microsatellite stable tumors by affecting cell invasion and motility. ATMIN is a potential prognostic factor in MSS CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Genomic instability is a hallmark of cancer, often stemming from DNA damage response (DDR) defects and replication stress.
  • Ataxia-telangiectasia mutated interactor (ATMIN) is a DDR pathway protein implicated in mismatch repair-proficient (microsatellite stability [MSS]) cancers.

Purpose of the Study:

  • To investigate the role and molecular mechanism of ATMIN in colorectal carcinoma (CRC) with MSS characteristics.
  • To evaluate ATMIN as a prognostic marker in MSS CRC.

Main Methods:

  • Analysis of ATMIN mRNA expression in CRC specimens.
  • In vitro experiments assessing the impact of ATMIN modulation on cancer cell invasion and motility.
  • Co-immunoprecipitation assays to elucidate molecular interactions.
  • High-throughput screening to identify signaling pathways involved.

Main Results:

  • ATMIN expression positively correlated with advanced stage, lymph node metastasis, and deeper invasion in MSS CRC.
  • Modulating ATMIN levels significantly affected cancer cell motility in vitro.
  • ATMIN was found to interact with PARP1, influencing the Wnt signaling pathway.
  • PARP1 inhibition counteracted the pro-invasive effects of ATMIN overexpression.

Conclusions:

  • ATMIN plays a significant role in regulating CRC progression, particularly in MSS tumors.
  • ATMIN influences cancer cell invasion and motility via the Wnt signaling pathway and PARP1.
  • ATMIN serves as a crucial prognostic factor for MSS colorectal carcinoma.

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