Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway

Abstract Despite advances in gastric cancer diagnosis and treatment, its prognosis remains poor owing to aggressive tumor progression and metastasis. As understanding the relevant molecular mechanisms is essential to effectively improve patient outcomes, we elucidated the role of Kindlin-1 in gastri...

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Main Authors: Jun-Ho Jang, Jiyoon Jung, Hyeon-Gu Kang, Woong Kim, Won-Jin Kim, Hana Lee, Ju Yeon Cho, Ran Hong, Jeong Won Kim, Joon-Yong Chung, Kyung-Hee Chun, Seok-Jun Kim
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86220-7
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author Jun-Ho Jang
Jiyoon Jung
Hyeon-Gu Kang
Woong Kim
Won-Jin Kim
Hana Lee
Ju Yeon Cho
Ran Hong
Jeong Won Kim
Joon-Yong Chung
Kyung-Hee Chun
Seok-Jun Kim
author_facet Jun-Ho Jang
Jiyoon Jung
Hyeon-Gu Kang
Woong Kim
Won-Jin Kim
Hana Lee
Ju Yeon Cho
Ran Hong
Jeong Won Kim
Joon-Yong Chung
Kyung-Hee Chun
Seok-Jun Kim
author_sort Jun-Ho Jang
collection DOAJ
description Abstract Despite advances in gastric cancer diagnosis and treatment, its prognosis remains poor owing to aggressive tumor progression and metastasis. As understanding the relevant molecular mechanisms is essential to effectively improve patient outcomes, we elucidated the role of Kindlin-1 in gastric cancer progression and metastasis. Kindlin-1 expression was analyzed in 359 gastric cancer tissue samples provided by Kangnam Sacred Heart Hospital and publicly available GSE datasets. Kindlin-1 showed significantly higher expression in gastric cancer tissues than that in normal tissues, and high Kindlin-1 expression was associated with poor prognosis. Further, the mRNA and protein expression of Kindlin-1 were high in gastric cancer cell lines, where they were associated with increased proliferation, migration, and invasion. Our findings demonstrated that Kindlin-1 regulated epithelial–mesenchymal transition-related genes through interaction with activated Wnt/β-catenin signaling. Notably, Kindlin-1 enhanced β-catenin expression and promoted its nuclear translocation from the cytoplasm, increasing TCF4 transcriptional activity and inducing gastric cancer progression and metastasis. Overall, these findings demonstrate that Kindlin-1 is upregulated in gastric cancer and activates Wnt/β-catenin signaling to promote cell proliferation and motility.
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spelling doaj-art-876728e09b2e43dfafea6e4ae071faf62025-01-26T12:31:46ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-025-86220-7Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathwayJun-Ho Jang0Jiyoon Jung1Hyeon-Gu Kang2Woong Kim3Won-Jin Kim4Hana Lee5Ju Yeon Cho6Ran Hong7Jeong Won Kim8Joon-Yong Chung9Kyung-Hee Chun10Seok-Jun Kim11Department of Integrative Biological Sciences and BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun UniversityDepartment of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of MedicineDepartment of Integrative Biological Sciences and BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun UniversityInstitute of Well-Aging Medicare and Chosun University G-LAMP Project Group, Chosun UniversityDepartment of Integrative Biological Sciences and BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun UniversityDepartment of Integrative Biological Sciences and BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun UniversityDepartment of Internal Medicine, College of Medicine, Chosun UniversityDepartment of Pathology, College of Medicine, Chosun UniversityDepartment of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of MedicineMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthDepartment of Biochemistry and Molecular Biology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineDepartment of Integrative Biological Sciences and BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun UniversityAbstract Despite advances in gastric cancer diagnosis and treatment, its prognosis remains poor owing to aggressive tumor progression and metastasis. As understanding the relevant molecular mechanisms is essential to effectively improve patient outcomes, we elucidated the role of Kindlin-1 in gastric cancer progression and metastasis. Kindlin-1 expression was analyzed in 359 gastric cancer tissue samples provided by Kangnam Sacred Heart Hospital and publicly available GSE datasets. Kindlin-1 showed significantly higher expression in gastric cancer tissues than that in normal tissues, and high Kindlin-1 expression was associated with poor prognosis. Further, the mRNA and protein expression of Kindlin-1 were high in gastric cancer cell lines, where they were associated with increased proliferation, migration, and invasion. Our findings demonstrated that Kindlin-1 regulated epithelial–mesenchymal transition-related genes through interaction with activated Wnt/β-catenin signaling. Notably, Kindlin-1 enhanced β-catenin expression and promoted its nuclear translocation from the cytoplasm, increasing TCF4 transcriptional activity and inducing gastric cancer progression and metastasis. Overall, these findings demonstrate that Kindlin-1 is upregulated in gastric cancer and activates Wnt/β-catenin signaling to promote cell proliferation and motility.https://doi.org/10.1038/s41598-025-86220-7Kindlin-1β-cateninCell proliferationCell motilityEpithelial–mesenchymal transitionGastric cancer
spellingShingle Jun-Ho Jang
Jiyoon Jung
Hyeon-Gu Kang
Woong Kim
Won-Jin Kim
Hana Lee
Ju Yeon Cho
Ran Hong
Jeong Won Kim
Joon-Yong Chung
Kyung-Hee Chun
Seok-Jun Kim
Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway
Scientific Reports
Kindlin-1
β-catenin
Cell proliferation
Cell motility
Epithelial–mesenchymal transition
Gastric cancer
title Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway
title_full Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway
title_fullStr Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway
title_full_unstemmed Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway
title_short Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway
title_sort kindlin 1 promotes gastric cancer cell motility through the wnt β catenin signaling pathway
topic Kindlin-1
β-catenin
Cell proliferation
Cell motility
Epithelial–mesenchymal transition
Gastric cancer
url https://doi.org/10.1038/s41598-025-86220-7
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