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Updated: Aug 28, 2025

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Published on: July 28, 2010
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.
Abstract:
Genomic instability is a key cancer indicator. It results from defects in the DNA damage response (DDR) and increased replication stress. Herein, we examined how ataxia-telangiectasia mutated interactor (ATMIN), a DDR pathway involved in mismatch repair-proficient (microsatellite stability [MSS]), acts in colorectal carcinoma (CRC). Firstly, ATMIN mRNA expression was detected in CRC specimens with MSS characteristics, and the effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were gauged in MSS cell lines. To understand the molecular mechanism, co-immunoprecipitation analyses in vitro were employed. Interestingly, ATMIN expression was positively correlated with advanced stages (P < .001), lymph node metastases (P = .002), and deeper invasion (P = .037) in MSS tumors; and significantly changed the cell motility in vitro. In the high-throughput analysis, ATMIN was found to act on the Wnt signaling pathway via PARP1. PAPR1 inhibition, in turn, significantly decreased invasion abilities resulting from ATMIN overexpression in cancer cell. Taken together, ATMIN, which alters the Wnt signaling pathway regulating CRC progression, plays as a crucial prognostic factor in MSS tumors.
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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