The lipogenic LXR-SREBF1 signaling pathway controls cancer cell DNA repair and apoptosis and is a vulnerable point of malignant tumors for cancer therapy.

Cell Death and Differentiation
Bo YangQuansheng Zhou

Abstract

Cancer cells are defective in DNA repair, so they experience increased DNA strand breaks, genome instability, gene mutagenesis, and tumorigenicity; however, multiple classic DNA repair genes and pathways are strongly activated in malignant tumor cells to compensate for the DNA repair deficiency and gain an apoptosis resistance. The mechanisms underlying this phenomenon in cancer are unclear. We speculate that a key DNA repair gene or signaling pathway in cancer has not yet been recognized. Here, we show that the lipogenic liver X receptor (LXR)-sterol response element binding factor-1 (SREBF1) axis controls the transcription of a key DNA repair gene polynucleotide kinase/phosphatase (PNKP), thereby governing cancer cell DNA repair and apoptosis. Notably, the PNKP levels were significantly reduced in 95% of human pancreatic cancer (PC) patients, particularly deep reduction for sixfold in all of the advanced-stage PC cases. PNKP is also deficient in three other types of cancer that we examined. In addition, the expression of LXRs and SREBF1 was significantly reduced in the tumor tissues from human PC patients compared with the adjacent normal tissues. The newly identified LXR-SREBF1-PNKP signaling pathway is deficient in PC, and ...Continue Reading

References

Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·R A DeBose-BoydM S Brown
May 3, 2002·Journal of Medicinal Chemistry·Jon L CollinsTimothy M Willson
Oct 7, 2004·Molecular Genetics and Metabolism·Keith A HouckThomas P Burris
Nov 15, 2012·Molecular Oncology·Letizia PorcelliAmalia Azzariti
May 16, 2013·PLoS Genetics·Aurélien J C PommierSilvère Baron
Apr 30, 2014·International Journal of Molecular Sciences·Chao LiQingguang Liu
Jul 9, 2014·Histochemistry and Cell Biology·Michael OstermanFei Li
Aug 15, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David KarnakMeredith A Morgan
Aug 16, 2014·Cell Death and Differentiation·V DerangèreC Rébé
Nov 25, 2014·Journal of Cellular Biochemistry·Shinji MiwaRobert M Hoffman
Jan 16, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yan SunYu Hu
Feb 27, 2015·Nature·Nicola WaddellSean M Grimmond
May 2, 2015·Cancer Research·Anchit Khanna
Nov 28, 2015·Basic Research in Cardiology·Megan V CannonRudolf A de Boer
Jan 13, 2016·Lipids in Health and Disease·Michela CodiniElisabetta Albi
Feb 26, 2016·Nature·Peter BaileySean M Grimmond
Mar 1, 2016·Cancer Treatment Reviews·Iris H LiuPamela L Kunz
Oct 18, 2016·Cancer Cell·Genaro R VillaPaul S Mischel
Apr 7, 2017·International Journal of Molecular Sciences·Mohammad Aslam Aslam KhanAjay Pratap Singh
Jun 7, 2017·Chemistry and Physics of Lipids·Gurdeep MarwarhaOthman Ghribi
Jan 27, 2018·Endocrine-related Cancer·Douglas A GibsonPhilippa T K Saunders
Feb 10, 2018·Current Medicinal Chemistry·Monika TomaTomasz Sliwinski

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
xenograft
pull-down
circular dichroism
surface plasmon resonance
flow cytometry
Assay
RNA-seq
Protein
electrophoresis

Software Mentioned

SPSS
GraphPad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.