PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1
Abstract Loss of ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, contributes to malignant progression in multiple cancers including non-small cell lung cancer (NSCLC). In the search for key genes mediating the aggressive phenotype caused by ARID1A loss, we analyzed 3 Gene Expression O...
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BMC
2024-01-01
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Series: | Biology Direct |
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Online Access: | https://doi.org/10.1186/s13062-024-00452-7 |
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author | Yuanliang Zheng Lixiang Zhang Kangliang Zhang Shenghao Wu Chichao Wang Risheng Huang Hongli Liao |
author_facet | Yuanliang Zheng Lixiang Zhang Kangliang Zhang Shenghao Wu Chichao Wang Risheng Huang Hongli Liao |
author_sort | Yuanliang Zheng |
collection | DOAJ |
description | Abstract Loss of ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, contributes to malignant progression in multiple cancers including non-small cell lung cancer (NSCLC). In the search for key genes mediating the aggressive phenotype caused by ARID1A loss, we analyzed 3 Gene Expression Omnibus (GEO) datasets that contain RNA sequencing data from ARID1A-depleted cancer cells. PLAU was identified as a common gene that was induced in different cancer cells upon ARID1A depletion. Overexpression of PLAU positively modulated NSCLC cell growth, colony formation, cisplatin resistance, and survival under serum deprivation. Moreover, enforced expression of PLAU enhanced tumorigenesis of NSCLC cells in nude mice. Mechanistically, PLAU interacted with TM4SF1 to promote the activation of Akt signaling. TM4SF1-overexpressing NSCLC cells resembled those with PLAU overepxression. Knockdown of TM4SF1 inhibited the growth and survival and increased cisplatin sensitivity in NSCLC cells. The interaction between PLAU and TM4SF1 led to the activation of Akt signaling that endowed ARID1A-depleted NSCLC cells with aggressive properties. In addition, treatment with anti-TM4SF1 neutralizing antibody reduced the growth, cisplatin resistance, and tumorigenesis of ARID1A-depleted NSCLC cells. Taken together, PLAU serves as a target gene of ARID1A and promotes NSCLC growth, survival, and cisplatin resistance by stabilizing TM4SF1. Targeting TM4SF1 may be a promising therapeutic strategy for ARID1A-mutated NSCLC. |
first_indexed | 2024-03-08T12:39:17Z |
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issn | 1745-6150 |
language | English |
last_indexed | 2024-03-08T12:39:17Z |
publishDate | 2024-01-01 |
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series | Biology Direct |
spelling | doaj.art-4e5310b7f616451cba9b6a4a362657202024-01-21T12:13:28ZengBMCBiology Direct1745-61502024-01-0119111410.1186/s13062-024-00452-7PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1Yuanliang Zheng0Lixiang Zhang1Kangliang Zhang2Shenghao Wu3Chichao Wang4Risheng Huang5Hongli Liao6Department of Thoracic Surgery, The Dingli Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai UniversityDepartment of Thoracic Surgery, The Dingli Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai UniversityDepartment of Central Lab, The Dingli Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai UniversityDepartment of Hematology and Chemotherapy, The Dingli Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai UniversityDepartment of Thoracic Surgery, The Dingli Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai UniversityDepartment of Thoracic Surgery, The Dingli Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai UniversityDepartment of Pathology, The Dingli Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai UniversityAbstract Loss of ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, contributes to malignant progression in multiple cancers including non-small cell lung cancer (NSCLC). In the search for key genes mediating the aggressive phenotype caused by ARID1A loss, we analyzed 3 Gene Expression Omnibus (GEO) datasets that contain RNA sequencing data from ARID1A-depleted cancer cells. PLAU was identified as a common gene that was induced in different cancer cells upon ARID1A depletion. Overexpression of PLAU positively modulated NSCLC cell growth, colony formation, cisplatin resistance, and survival under serum deprivation. Moreover, enforced expression of PLAU enhanced tumorigenesis of NSCLC cells in nude mice. Mechanistically, PLAU interacted with TM4SF1 to promote the activation of Akt signaling. TM4SF1-overexpressing NSCLC cells resembled those with PLAU overepxression. Knockdown of TM4SF1 inhibited the growth and survival and increased cisplatin sensitivity in NSCLC cells. The interaction between PLAU and TM4SF1 led to the activation of Akt signaling that endowed ARID1A-depleted NSCLC cells with aggressive properties. In addition, treatment with anti-TM4SF1 neutralizing antibody reduced the growth, cisplatin resistance, and tumorigenesis of ARID1A-depleted NSCLC cells. Taken together, PLAU serves as a target gene of ARID1A and promotes NSCLC growth, survival, and cisplatin resistance by stabilizing TM4SF1. Targeting TM4SF1 may be a promising therapeutic strategy for ARID1A-mutated NSCLC.https://doi.org/10.1186/s13062-024-00452-7ARID1AChemoresistanceGrowthLung cancerPLAU |
spellingShingle | Yuanliang Zheng Lixiang Zhang Kangliang Zhang Shenghao Wu Chichao Wang Risheng Huang Hongli Liao PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1 Biology Direct ARID1A Chemoresistance Growth Lung cancer PLAU |
title | PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1 |
title_full | PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1 |
title_fullStr | PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1 |
title_full_unstemmed | PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1 |
title_short | PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1 |
title_sort | plau promotes growth and attenuates cisplatin chemosensitivity in arid1a depleted non small cell lung cancer through interaction with tm4sf1 |
topic | ARID1A Chemoresistance Growth Lung cancer PLAU |
url | https://doi.org/10.1186/s13062-024-00452-7 |
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