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TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer

KRAS mutation is very common in pancreatic cancer. How pancreatic cancer cells overcome oncogene-induced senescence is not fully understood. Our previous studies showed that up-regulation of TFCP2 (transcription factor CP2) in pancreatic cancer promoted the growth and metastasis of pancreatic cancer...

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Autores principales: Zhang, Dexiang, Lu, Pinxiang, Zhu, Kaihua, Wu, Haixia, Dai, Yuedi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599447/
https://www.ncbi.nlm.nih.gov/pubmed/34804919
http://dx.doi.org/10.3389/fonc.2021.724437
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author Zhang, Dexiang
Lu, Pinxiang
Zhu, Kaihua
Wu, Haixia
Dai, Yuedi
author_facet Zhang, Dexiang
Lu, Pinxiang
Zhu, Kaihua
Wu, Haixia
Dai, Yuedi
author_sort Zhang, Dexiang
collection PubMed
description KRAS mutation is very common in pancreatic cancer. How pancreatic cancer cells overcome oncogene-induced senescence is not fully understood. Our previous studies showed that up-regulation of TFCP2 (transcription factor CP2) in pancreatic cancer promoted the growth and metastasis of pancreatic cancer cells. However, whether TFCP2 plays an important role in pancreatic cancer cell senescence is not clear. In this study, we found upregulation of TFCP2 expression in pancreatic cancer was associated with KRAS mutation. Overexpression of TFCP2 inhibited cell senescence. Knockdown of TFCP2 promoted cell senescence. Mechanistically, the interaction between TFCP2 and SREBP2 (sterol regulatory element binding transcription factor 2) synergistically activated the expression of HMGCR, a rate-limiting enzyme in cholesterol synthesis, and statins could reverse the inhibitory effect of TFCP2 on senescence. In conclusion, our study reveals a new mechanism underlying the TFCP2 regulation of pancreatic cancer cell senescence, providing a new target for the treatment of pancreatic cancer.
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spelling pubmed-85994472021-11-19 TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer Zhang, Dexiang Lu, Pinxiang Zhu, Kaihua Wu, Haixia Dai, Yuedi Front Oncol Oncology KRAS mutation is very common in pancreatic cancer. How pancreatic cancer cells overcome oncogene-induced senescence is not fully understood. Our previous studies showed that up-regulation of TFCP2 (transcription factor CP2) in pancreatic cancer promoted the growth and metastasis of pancreatic cancer cells. However, whether TFCP2 plays an important role in pancreatic cancer cell senescence is not clear. In this study, we found upregulation of TFCP2 expression in pancreatic cancer was associated with KRAS mutation. Overexpression of TFCP2 inhibited cell senescence. Knockdown of TFCP2 promoted cell senescence. Mechanistically, the interaction between TFCP2 and SREBP2 (sterol regulatory element binding transcription factor 2) synergistically activated the expression of HMGCR, a rate-limiting enzyme in cholesterol synthesis, and statins could reverse the inhibitory effect of TFCP2 on senescence. In conclusion, our study reveals a new mechanism underlying the TFCP2 regulation of pancreatic cancer cell senescence, providing a new target for the treatment of pancreatic cancer. Frontiers Media S.A. 2021-11-04 /pmc/articles/PMC8599447/ /pubmed/34804919 http://dx.doi.org/10.3389/fonc.2021.724437 Text en Copyright © 2021 Zhang, Lu, Zhu, Wu and Dai https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhang, Dexiang
Lu, Pinxiang
Zhu, Kaihua
Wu, Haixia
Dai, Yuedi
TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer
title TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer
title_full TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer
title_fullStr TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer
title_full_unstemmed TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer
title_short TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer
title_sort tfcp2 overcomes senescence by cooperating with srebp2 to activate cholesterol synthesis in pancreatic cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599447/
https://www.ncbi.nlm.nih.gov/pubmed/34804919
http://dx.doi.org/10.3389/fonc.2021.724437
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