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TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC

TM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, th...

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Autores principales: Yang, Si-bo, Zhou, Zi-han, Lei, Jin, Li, Xiao-wen, Chen, Qian, Li, Bo, Zhang, Ye-wei, Ge, Yu-zhen, Zuo, Shi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111829/
https://www.ncbi.nlm.nih.gov/pubmed/37069693
http://dx.doi.org/10.1186/s13062-023-00376-8
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author Yang, Si-bo
Zhou, Zi-han
Lei, Jin
Li, Xiao-wen
Chen, Qian
Li, Bo
Zhang, Ye-wei
Ge, Yu-zhen
Zuo, Shi
author_facet Yang, Si-bo
Zhou, Zi-han
Lei, Jin
Li, Xiao-wen
Chen, Qian
Li, Bo
Zhang, Ye-wei
Ge, Yu-zhen
Zuo, Shi
author_sort Yang, Si-bo
collection PubMed
description TM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, the effect of TM4SF1 on cancer stemness in hepatocellular carcinoma (HCC) and its molecular basis are yet to be reported. We found through abundant in vitro and in vivo experiments which the expression of TM4SF1 was positively correlated with the progression and cancer stemness of HCC. We identified the downstream protein MYH9 of TM4SF1 and its final regulatory target NOTCH pathway using bioinformatics analysis and protein mass spectrometry. We cultivated a Lenvatinib-resistant strain from HCC cells to examine the relationship between cancer stemness and tumor drug resistance. The study confirmed that TM4SF1 could regulate the NOTCH pathway by upregulating MYH9, thus promoting cancer stemness and Lenvatinib resistance in HCC. This study not only provided a new idea for the pathogenesis of HCC but also confirmed that TM4SF1 might become a new intervention point to improve the clinical efficacy of Lenvatinib in treating HCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00376-8.
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spelling pubmed-101118292023-04-19 TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC Yang, Si-bo Zhou, Zi-han Lei, Jin Li, Xiao-wen Chen, Qian Li, Bo Zhang, Ye-wei Ge, Yu-zhen Zuo, Shi Biol Direct Research TM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, the effect of TM4SF1 on cancer stemness in hepatocellular carcinoma (HCC) and its molecular basis are yet to be reported. We found through abundant in vitro and in vivo experiments which the expression of TM4SF1 was positively correlated with the progression and cancer stemness of HCC. We identified the downstream protein MYH9 of TM4SF1 and its final regulatory target NOTCH pathway using bioinformatics analysis and protein mass spectrometry. We cultivated a Lenvatinib-resistant strain from HCC cells to examine the relationship between cancer stemness and tumor drug resistance. The study confirmed that TM4SF1 could regulate the NOTCH pathway by upregulating MYH9, thus promoting cancer stemness and Lenvatinib resistance in HCC. This study not only provided a new idea for the pathogenesis of HCC but also confirmed that TM4SF1 might become a new intervention point to improve the clinical efficacy of Lenvatinib in treating HCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00376-8. BioMed Central 2023-04-17 /pmc/articles/PMC10111829/ /pubmed/37069693 http://dx.doi.org/10.1186/s13062-023-00376-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Si-bo
Zhou, Zi-han
Lei, Jin
Li, Xiao-wen
Chen, Qian
Li, Bo
Zhang, Ye-wei
Ge, Yu-zhen
Zuo, Shi
TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC
title TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC
title_full TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC
title_fullStr TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC
title_full_unstemmed TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC
title_short TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC
title_sort tm4sf1 upregulates myh9 to activate the notch pathway to promote cancer stemness and lenvatinib resistance in hcc
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111829/
https://www.ncbi.nlm.nih.gov/pubmed/37069693
http://dx.doi.org/10.1186/s13062-023-00376-8
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