ARID1A overexpression inhibits colorectal cancer cell migration through the regulation of epithelial‑mesenchymal transition - Abstract

Q: Why is EMT important in colorectal cancer metastasis?

EMT influences tumor cell metastasis, and metastatic CRC strongly contributes to cancer-related mortality and poor patient prognosis.

Q: How was ARID1A studied in this research?

ARID1A loss in CRC tissues was assessed by immunohistochemistry, and ARID1A-overexpressing SW48 cells were created using lentiviruses carrying full-length human ARID1A.

Q: What effects did ARID1A overexpression have on EMT-related markers and migration?

ARID1A overexpression promoted junction molecules such as ZO-1 and E-cadherin while reducing vimentin, and it suppressed cell motility and migratory capabilities, reversing EMT-like phenotypes.

Sep 21, 2026

Uploaded by Levi

Advancement of tumor metastasis is closely tied to epithelial-to-mesenchymal transition (EMT), a key driver of colorectal cancer (CRC) mortality. AT-rich interactive domain-containing protein 1A (ARID1A), a tumor suppressor often lost by loss-of-function mutations in metastatic CRC, has unclear molecular links to EMT. This study examined ARID1A loss in CRC patient tissues via immunohistochemistry and generated ARID1A-overexpressing SW48 cells using lentiviruses to test EMT regulation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

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Abstract

Introduction

Background on CRC burden and metastasis

Role of EMT and ARID1A in cancer biology

Molecular Medicine rePorTS 30: 201, 2024 ARID1A overexpression inhibits colorectal cancer cell migration through the regulation of epithelial‑mesenchymal transition SASITHORN WANNA‑UDOM 1 , SIRIPATALUKSANASUWAN2,3 , KeeraKarn SoMSuan2,3 , WARIYAMONGKOLWAT 1 and NATTHIYASAKULSAK 1,4 1Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand; 2School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand; 3Cancer and Immunology Research Unit, Mae Fah Luang University, Chiang Rai 57100, Thailand; 4Faculty of Medicine, Praboromarajchanok Institute, Ministry of Public Health, Nonthaburi 11000, Thailand Received May 3, 2024; Accepted August 9, 2024 DOI: 10. 3892/mmr.2024.13325 Abstract. The advancement of tumor cell metastasis is significantly influenced by epithelial‑to‑mesenchymal transi‑ tion (EMT), and metastasis is a prominent contributor to the mortality of patients diagnosed with colorectal cancer (CRC) . AT‑rich interactive domain‑containing protein 1A (ARID1A), which acts as a tumor suppressor, frequently exhibits a loss‑of‑function mutation in metastatic CRC tissues. However, the underlying molecular mechanisms of ARID1A relating to EMT remain poorly understood. The present study aimed to clarify the association between ARID1A and eMT regulation in human crc cells. The investigation into the loss of ARID1A expression in tissues from patients with CRC was performed using immunohistochemistry. Furthermore, ARID1A‑overexpressing SW48 cells were established using lentiviruses carrying human full‑length ARID1A. The results revealed that overexpression of ARID1A induced cellular morphological changes by promoting the tight junction molecule zonula occludens 1 (ZO‑1) and the adherens junction molecule E‑cadherin, whereas it decreased the intermediate filament protein vimentin . The results of reverse transcription‑quantitative PCR also confirmed that ARID1A overexpression upregulated the mRNA expres‑ sion levels of TJP1/ZO‑1 and CDH1/ E‑cadherin, and downregulated VIM/vimentin and zinc finger E‑box binding homeobox 1 expression, which are considered epithelial and mesenchymal markers, respectively. In addition, the overex‑ pression of ARID1A in CRC cells resulted in a suppression of cell motility and migratory capabilities. The present study Correspondence to: Dr Natthiya Sakulsak, Faculty of Medicine, Praboromarajchanok Institute, Ministry of Public Health, 47/99 Building 7, Tiwanon Road, Talad Kwan, Mueang, Nonthaburi 11000, Thailand E‑[mail: natthiyak@nu.ac.th](mail: natthiyak@nu.ac.th) , [natthiyas@pi.ac.th](natthiyas@pi.ac.th) Key words: colorectal cancer, AT‑rich interactive domain‑ containing protein 1A, epithelial‑mesenchymal transition, epithelial‑ mesenchymal transition‑related markers, cell migration also demonstrated that the tumor suppressor ARID1A was commonly absent in CRC tissues. Notably, ARID1A overex‑ pression could reverse the EMT‑like phenotype and inhibit cell migration through alterations in EMT‑related markers, leading to the inhibition of malignant progression. In conclu‑ sion, ARID1A may serve as a biomarker and therapeutic target in the clinical management of metastatic crc. Introduction colorectal cancer (crc) is a common cause of cancer morbidity and mortality; it is the third most frequently diag‑ nosed malignancy worldwide and the second most common cause of cancer‑related mortality (1‑3) . According to global cancer statistics, >1. 85 million new cases ofCRC (9. 8% of total cancer cases) and an estimated 850,000 CRC‑related deaths (9 . 2% of total cancer‑related deaths) occurred in 2020 (2,4) . Among patients with CRC, 20% have metastatic CRC and 40% present with recurrence after previous localized disease treatment. Notably, prognosis of metastatic CRC is poor, with a 5‑year survival rate of <20%(5), and these patients often develop resistance to systemic therapy. Moreover, 35‑40% of patients with KRAS and NRAS gene mutat

FAQs

Why is EMT important in colorectal cancer metastasis?

EMT influences tumor cell metastasis, and metastatic CRC strongly contributes to cancer-related mortality and poor patient prognosis.

How was ARID1A studied in this research?

ARID1A loss in CRC tissues was assessed by immunohistochemistry, and ARID1A-overexpressing SW48 cells were created using lentiviruses carrying full-length human ARID1A.

What effects did ARID1A overexpression have on EMT-related markers and migration?

ARID1A overexpression promoted junction molecules such as ZO-1 and E-cadherin while reducing vimentin, and it suppressed cell motility and migratory capabilities, reversing EMT-like phenotypes.

Sep 21, 2026

Uploaded by Levi