---
title: "NECTIN2 promotes migration and invasion in MDA-MB-231 TNBC via LIMK1-linked cytoskeletal remodeling"
id: "pubmed-42664293"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42664293"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42664293/"
doi: "10.1371/journal.pone.0356726"
published_at: "2026-08-28T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# NECTIN2 promotes migration and invasion in MDA-MB-231 TNBC via LIMK1-linked cytoskeletal remodeling
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42664293
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42664293/)
- **DOI:** [10.1371/journal.pone.0356726](https://doi.org/10.1371%2Fjournal.pone.0356726)
- **Published At:** 2026-08-28T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- NECTIN2, an immunoglobulin-like cell adhesion and immune-regulatory glycoprotein, is **overexpressed in breast cancer** versus normal tissue based on publicly available data sets reported by the authors. - Elevated NECTIN2 expression correlated with **worse recurrence-free survival** specifically in patients with triple-negative breast cancer (TNBC) in the analyzed data. - Among TNBC cell lines examined, **MDA-MB-231** cells showed the highest NECTIN2 expression at both mRNA and protein levels, consistent with a more aggressive phenotype. - The authors silenced NECTIN2 in MDA-MB-231 and MDA-MB-468 cells and observed a modest reduction in viability over time in NECTIN2-depleted MDA-MB-231 cells, with no significant viability change in MDA-MB-468 cells. - NECTIN2 depletion produced a **significant reduction in migration and invasion** in MDA-MB-231 cells but did not alter these phenotypes in MDA-MB-468 cells, indicating a cell line–specific effect. - Gene expression profiling after NECTIN2 knockdown indicated decreased expression of **LIMK1**, a regulator of actin cytoskeleton dynamics and cell motility. - Ectopic re-expression of LIMK1 in NECTIN2-deficient MDA-MB-231 cells partially rescued migratory capacity and induced partial **epithelial–mesenchymal transition (EMT)**-like marker changes: decreased E-cadherin and ZO-1, increased fibronectin and Slug. - The data support a model in which NECTIN2 contributes to migratory and invasive phenotypes in MDA-MB-231 cells potentially via **LIMK1-associated cytoskeletal remodeling** and EMT-related marker modulation. - The authors emphasize that this mechanism appears to be context-dependent and may not apply uniformly across TNBC subtypes; further investigation is required.
## Clinical Analysis & Structured Key Points
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NECTIN2 depletion impairs migration and invasion in MDA-MB-231 breast cancer cells through LIMK1-associated cytoskeletal remodeling [Phatchanat Klaihmon](https://pubmed.ncbi.nlm.nih.gov/?term=Klaihmon+P&cauthor_id=42664293)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-1 "Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-2 "Molecular Cancer Therapeutics Research Group, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Pattaratorn Muangtate](https://pubmed.ncbi.nlm.nih.gov/?term=Muangtate+P&cauthor_id=42664293)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-3 "Master of Science Program in Molecular Genetics and Genetic Engineering, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-4 "Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand."), [Sudarat Thongphayong](https://pubmed.ncbi.nlm.nih.gov/?term=Thongphayong+S&cauthor_id=42664293)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-4 "Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-5 "Doctor of Philosophy Program in Systems Biosciences, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand."), [Puretat Saetan](https://pubmed.ncbi.nlm.nih.gov/?term=Saetan+P&cauthor_id=42664293)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-1 "Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Supasorn Chanthateyanonth](https://pubmed.ncbi.nlm.nih.gov/?term=Chanthateyanonth+S&cauthor_id=42664293)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-1 "Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-2 "Molecular Cancer Therapeutics Research Group, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Chanitra Thuwajit](https://pubmed.ncbi.nlm.nih.gov/?term=Thuwajit+C&cauthor_id=42664293)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-6 "Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Surapol Issargrisil](https://pubmed.ncbi.nlm.nih.gov/?term=Issargrisil+S&cauthor_id=42664293)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-1 "Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Phatchariya Phannasil](https://pubmed.ncbi.nlm.nih.gov/?term=Phannasil+P&cauthor_id=42664293)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#full-view-affiliation-4 "Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.") Affiliations Expand ### Affiliations * 1 Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. * 2 Molecular Cancer Therapeutics Research Group, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. * 3 Master of Science Program in Molecular Genetics and Genetic Engineering, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand. * 4 Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand. * 5 Doctor of Philosophy Program in Systems Biosciences, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand. * 6 Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. * PMID: **42664293** * DOI: [ 10.1371/journal.pone.0356726 ](https://doi.org/10.1371/journal.pone.0356726) Item in Clipboard # NECTIN2 depletion impairs migration and invasion in MDA-MB-231 breast cancer cells through LIMK1-associated cytoskeletal remodeling Phatchanat Klaihmon et al. PLoS One. 2026. Show details Display options Display options Format Abstract PubMed PMID PLoS One Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22PLoS+One%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22PLoS+One%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664293/) . 2026 Aug 28;21(8):e0356726. doi: 10.1371/journal.pone.0356726. eCollection 2026. ### Authors [Phatchanat Klaihmon](https://pubmed.ncbi.nlm.nih.gov/?term=Klaihmon+P&cauthor_id=42664293)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-1 "Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-2 "Molecular Cancer Therapeutics Research Group, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Pattaratorn Muangtate](https://pubmed.ncbi.nlm.nih.gov/?term=Muangtate+P&cauthor_id=42664293)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-3 "Master of Science Program in Molecular Genetics and Genetic Engineering, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-4 "Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand."), [Sudarat Thongphayong](https://pubmed.ncbi.nlm.nih.gov/?term=Thongphayong+S&cauthor_id=42664293)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-4 "Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-5 "Doctor of Philosophy Program in Systems Biosciences, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand."), [Puretat Saetan](https://pubmed.ncbi.nlm.nih.gov/?term=Saetan+P&cauthor_id=42664293)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-1 "Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Supasorn Chanthateyanonth](https://pubmed.ncbi.nlm.nih.gov/?term=Chanthateyanonth+S&cauthor_id=42664293)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-1 "Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-2 "Molecular Cancer Therapeutics Research Group, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Chanitra Thuwajit](https://pubmed.ncbi.nlm.nih.gov/?term=Thuwajit+C&cauthor_id=42664293)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-6 "Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Surapol Issargrisil](https://pubmed.ncbi.nlm.nih.gov/?term=Issargrisil+S&cauthor_id=42664293)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-1 "Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand."), [Phatchariya Phannasil](https://pubmed.ncbi.nlm.nih.gov/?term=Phannasil+P&cauthor_id=42664293)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42664293/#short-view-affiliation-4 "Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.") ### Affiliations * 1 Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. * 2 Molecular Cancer Therapeutics Research Group, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. * 3 Master of Science Program in Molecular Genetics and Genetic Engineering, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand. * 4 Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand. * 5 Doctor of Philosophy Program in Systems Biosciences, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand. * 6 Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. * PMID: **42664293** * DOI: [ 10.1371/journal.pone.0356726 ](https://doi.org/10.1371/journal.pone.0356726) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Breast cancer (BC) is the most commonly diagnosed malignancy in women, with triple-negative breast cancer (TNBC) representing the most aggressive subtype that is associated with poor clinical outcomes. Identifying novel biomarkers or therapeutic targets is therefore of great importance. Nectin cell adhesion molecule-2 (NECTIN2) is an immunoglobulin-like glycoprotein involved in cell adhesion and immune regulation that is highly expressed in several cancers but its role in the progression of BC is unclear. Using publicly available data sets, we found that NECTIN2 expression is elevated in BC compared to normal tissues and is associated with poorer recurrence-free survival in TNBC patients. Among TNBC cell lines, MDA-MB-231 cells exhibited the highest expression of NECTIN2 at gene and protein levels, consistent with a more aggressive phenotype. To investigate its functional role, we silenced NECTIN2 in MDA-MB-231 and MDA-MB-468 cells. Relative cell viability was modestly reduced in NECTIN2-depleted MDA-MB-231 cells at later time points, but no significant changes were observed in MDA-MB-468 cells. Interestingly, NECTIN2 depletion significantly reduced migration and invasion in MDA-MB-231 cells, but not in MDA-MB-468 cells. Given this cell line-specific effect, subsequent mechanistic investigations focused on the MDA-MB-231 model. Gene expression profiling suggested a reduction in LIMK1, a regulator of cytoskeletal dynamics and cell motility, following NECTIN2 depletion. Furthermore, ectopic expression of LIMK1 in NECTIN2-deficient MDA-MB-231 cells partially restored migratory capacity and was associated with partial epithelial-mesenchymal transition (EMT)-like changes, including a decrease in E-cadherin and ZO-1, and a higher level of fibronectin and Slug. Collectively, these findings suggest that NECTIN2 contributes to migratory and invasive phenotypes in MDA-MB-231 cells, potentially through LIMK1-associated cytoskeletal remodeling and EMT-related marker changes. However, this mechanism requires further investigation because it appears to be context-dependent and may not be universally applicable across TNBC subtypes. Copyright: © 2026 Klaihmon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement The authors have declared that no competing interests exist. ## MeSH terms * Cell Line, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%2C+Tumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664293/) * Cell Movement* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Movement%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Movement) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664293/) * Cytoskeleton* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cytoskeleton%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cytoskeleton) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664293/) * Epithelial-Mesenchymal Transition Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Epithelial-Mesenchymal+Transition%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Epithelial-Mesenchymal+Transition) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664293/) * Female Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Female) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664293/) * Gene Expression Regulation, Neoplastic Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gene+Expression+Regulation%2C+Neoplastic%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Gene+Expression+Regulation%2C+Neoplastic) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664293/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664293/) * Lim Kinases* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Lim+Kinases%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=de
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