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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Nature Portfolio
2025-01-01
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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. |
format | Article |
id | doaj-art-876728e09b2e43dfafea6e4ae071faf6 |
institution | Kabale University |
issn | 2045-2322 |
language | English |
publishDate | 2025-01-01 |
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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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