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:	Dexiang Zhang, Pinxiang Lu, Kaihua Zhu, Haixia Wu, Yuedi Dai
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	pancreatic cancer cell senescence cholesterol synthesis TFCP2 SREBP2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f678d0af0f334452ab13a748b4f421a9
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spelling	oai:doaj.org-article:f678d0af0f334452ab13a748b4f421a92021-11-04T05:41:08ZTFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer2234-943X10.3389/fonc.2021.724437https://doaj.org/article/f678d0af0f334452ab13a748b4f421a92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.724437/fullhttps://doaj.org/toc/2234-943XKRAS 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.Dexiang ZhangPinxiang LuKaihua ZhuHaixia WuYuedi DaiFrontiers Media S.A.articlepancreatic cancercell senescencecholesterol synthesisTFCP2SREBP2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreatic cancer cell senescence cholesterol synthesis TFCP2 SREBP2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	pancreatic cancer cell senescence cholesterol synthesis TFCP2 SREBP2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Dexiang Zhang Pinxiang Lu Kaihua Zhu Haixia Wu Yuedi Dai TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer
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.
format	article
author	Dexiang Zhang Pinxiang Lu Kaihua Zhu Haixia Wu Yuedi Dai
author_facet	Dexiang Zhang Pinxiang Lu Kaihua Zhu Haixia Wu Yuedi Dai
author_sort	Dexiang Zhang
title	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_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_sort	tfcp2 overcomes senescence by cooperating with srebp2 to activate cholesterol synthesis in pancreatic cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f678d0af0f334452ab13a748b4f421a9
work_keys_str_mv	AT dexiangzhang tfcp2overcomessenescencebycooperatingwithsrebp2toactivatecholesterolsynthesisinpancreaticcancer AT pinxianglu tfcp2overcomessenescencebycooperatingwithsrebp2toactivatecholesterolsynthesisinpancreaticcancer AT kaihuazhu tfcp2overcomessenescencebycooperatingwithsrebp2toactivatecholesterolsynthesisinpancreaticcancer AT haixiawu tfcp2overcomessenescencebycooperatingwithsrebp2toactivatecholesterolsynthesisinpancreaticcancer AT yuedidai tfcp2overcomessenescencebycooperatingwithsrebp2toactivatecholesterolsynthesisinpancreaticcancer
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TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer

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