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ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway

Pancreatic cancer (PC) is one of the malignant tumors with the worst prognosis worldwide because of a lack of early diagnostic markers and efficient therapies. Integrin, beta-like 1 (ITGBL1) is a β-integrin-related extracellular matrix protein and is reported to promote progression of some types of...

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Autores principales: Du, Tiancong, Zhang, Ke, Zhang, Zhongbo, Guo, Aijia, Yu, Guilin, Xu, Yuanhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Associação Brasileira de Divulgação Científica 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113530/
https://www.ncbi.nlm.nih.gov/pubmed/35584452
http://dx.doi.org/10.1590/1414-431X2022e11989
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author Du, Tiancong
Zhang, Ke
Zhang, Zhongbo
Guo, Aijia
Yu, Guilin
Xu, Yuanhong
author_facet Du, Tiancong
Zhang, Ke
Zhang, Zhongbo
Guo, Aijia
Yu, Guilin
Xu, Yuanhong
author_sort Du, Tiancong
collection PubMed
description Pancreatic cancer (PC) is one of the malignant tumors with the worst prognosis worldwide because of a lack of early diagnostic markers and efficient therapies. Integrin, beta-like 1 (ITGBL1) is a β-integrin-related extracellular matrix protein and is reported to promote progression of some types of cancer. Nevertheless, the function of ITGBL1 in PC is still not clear. Herein, we found that ITGBL1 was highly expressed in PC tissues compared to normal tissues (P<0.05) and PC patients with higher TGBL1 expression showed worse prognosis. PANC-1 and AsPC-1 cells were used for gain/loss-of-function experiments. We found that ITGBL1-silenced cells exhibited decreased proliferation, migration, and invasion abilities and delayed cell cycle, whereas ITGBL1 overexpression reversed these malignant behaviors. ITGBL1 was also demonstrated to activate the TGF-β/Smad pathway, a key signaling pathway in PC progression. Additionally, ITGBL1 expression was found to be suppressed by a suppressor of PC progression, c-Jun dimerization protein 2 (JDP2). Results of dual-luciferase assay indicated that transcription factor JDP2 could inhibit TGBL1 promoter activity. ITGBL1 overexpression inversed the effects of JDP2 up-regulation on cell function. Collectively, we concluded that ITGBL1 may be transcriptionally suppressed by JDP2 and promote PC progression through the TGF-β/Smad pathway, indicating that ITGBL1 may have therapeutic potential for the treatment of PC.
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spelling pubmed-91135302022-05-31 ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway Du, Tiancong Zhang, Ke Zhang, Zhongbo Guo, Aijia Yu, Guilin Xu, Yuanhong Braz J Med Biol Res Research Article Pancreatic cancer (PC) is one of the malignant tumors with the worst prognosis worldwide because of a lack of early diagnostic markers and efficient therapies. Integrin, beta-like 1 (ITGBL1) is a β-integrin-related extracellular matrix protein and is reported to promote progression of some types of cancer. Nevertheless, the function of ITGBL1 in PC is still not clear. Herein, we found that ITGBL1 was highly expressed in PC tissues compared to normal tissues (P<0.05) and PC patients with higher TGBL1 expression showed worse prognosis. PANC-1 and AsPC-1 cells were used for gain/loss-of-function experiments. We found that ITGBL1-silenced cells exhibited decreased proliferation, migration, and invasion abilities and delayed cell cycle, whereas ITGBL1 overexpression reversed these malignant behaviors. ITGBL1 was also demonstrated to activate the TGF-β/Smad pathway, a key signaling pathway in PC progression. Additionally, ITGBL1 expression was found to be suppressed by a suppressor of PC progression, c-Jun dimerization protein 2 (JDP2). Results of dual-luciferase assay indicated that transcription factor JDP2 could inhibit TGBL1 promoter activity. ITGBL1 overexpression inversed the effects of JDP2 up-regulation on cell function. Collectively, we concluded that ITGBL1 may be transcriptionally suppressed by JDP2 and promote PC progression through the TGF-β/Smad pathway, indicating that ITGBL1 may have therapeutic potential for the treatment of PC. Associação Brasileira de Divulgação Científica 2022-05-16 /pmc/articles/PMC9113530/ /pubmed/35584452 http://dx.doi.org/10.1590/1414-431X2022e11989 Text en https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Du, Tiancong
Zhang, Ke
Zhang, Zhongbo
Guo, Aijia
Yu, Guilin
Xu, Yuanhong
ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway
title ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway
title_full ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway
title_fullStr ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway
title_full_unstemmed ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway
title_short ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway
title_sort itgbl1 transcriptionally inhibited by jdp2 promotes the development of pancreatic cancer through the tgf-beta/smad pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113530/
https://www.ncbi.nlm.nih.gov/pubmed/35584452
http://dx.doi.org/10.1590/1414-431X2022e11989
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