Related Experiment Video

Updated: Nov 1, 2025

The Soft Agar Colony Formation Assay
08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

112.7K

ATMIN Suppresses Metastasis by Altering the WNT-Signaling Pathway via PARP1 in MSI-High 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.

Annals of Surgical Oncology
|June 20, 2021
PubMed
Abstract

Insights

Ataxia-telangiectasia mutated interactor (ATMIN) plays a key role in colorectal cancer (CRC) progression. Lower ATMIN levels correlate with advanced disease, and targeting PARP1 may offer new therapeutic strategies for MSI-high CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • DNA damage response (DDR) is crucial for cellular integrity.
  • Mismatch repair-deficient (MSI-high) colorectal carcinoma (CRC) involves impaired DDR pathways.
  • Ataxia-telangiectasia mutated interactor (ATMIN) is implicated in DDR pathways within MSI-high CRC.

Purpose of the Study:

  • To investigate the role of ATMIN in MSI-high colorectal carcinoma.
  • To explore the relationship between ATMIN expression and tumor progression.
  • To elucidate the molecular mechanisms involving ATMIN in CRC metastasis.

Main Methods:

  • ATMIN mRNA expression was quantified in CRC specimens.
  • In vitro and in vivo assays assessed the impact of ATMIN modulation on cell invasion and metastasis.
  • Coimmunoprecipitation identified protein-protein interactions.
  • Microarray and gene set enrichment analysis revealed signaling pathway involvement.

Main Results:

  • Reduced ATMIN expression correlated with advanced disease stage, lymph node metastasis, and deeper tumor invasion in MSI-high CRC.
  • ATMIN knockdown enhanced cancer cell motility and invasion.
  • ATMIN influences the Wnt signaling pathway via PARP1 and β-catenin/TCF4 binding.
  • PARP1 inhibition reduced metastasis in ATMIN-knockdown cells.

Conclusions:

  • ATMIN is a critical factor in MSI-high CRC progression.
  • The study highlights a novel ATMIN-PARP1-Wnt signaling axis.
  • Findings support further clinical trials of PARP1 inhibitors for MSI-high CRC.

More Related Videos

An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

35.5K
In vitro Organoid Culture of Primary Mouse Colon Tumors07:33

In vitro Organoid Culture of Primary Mouse Colon Tumors

Published on: May 17, 2013

35.4K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.8K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
9.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.0K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.7K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.9K