Fatostatin induces pro- and anti-apoptotic lipid accumulation in breast cancer

Oncogenesis
Viktor BrovkovychJonna Frasor

Abstract

Given the dependence of cancers on de novo lipogenesis, we tested the effect of fatostatin, a small molecule thought to target this pathway by blocking activation of SREBP transcription factors, in breast cancer cell lines and xenograft tumors. We found that estrogen receptor (ER) positive cells were more sensitive to fatostatin than ER negative cells and responded with cell cycle arrest and apoptosis. Surprisingly, we found that rather than inhibiting lipogenesis, fatostatin caused an accumulation of lipids as a response to endoplasmic reticulum stress rather than inhibition of SREBP activity. In particular, ceramide and dihydroceramide levels increased and contributed to the apoptotic effects of fatostatin. In addition, an accumulation of triacylglycerides (TAGs), particularly those containing polyunsaturated fatty acids (PUFAs), was also observed as a result of elevated diacylglycerol transferase activity. Blocking PUFA-TAG production enhanced the apoptotic effect of fatostatin, suggesting that these lipids play a protective role and limit fatostatin response. Together, these findings indicate that the ability of breast cancer cells to respond to fatostatin depends on induction of endoplasmic reticulum stress and subsequent ...Continue Reading

References

Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·F P KuhajdaG R Pasternack
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Laura L ListenbergerJean E Schaffer
Jun 14, 2003·The Journal of Biological Chemistry·Serge HardyYves Langelier
Nov 10, 2004·Biochemistry·Alan SaghatelianBenjamin F Cravatt
Mar 3, 2006·Molecular and Cellular Biochemistry·Leslie C Costello, Renty B Franklin
Jun 17, 2006·Cancer Research·Francis P Kuhajda
Sep 21, 2007·Nature Reviews. Cancer·Javier A Menendez, Ruth Lupu
Oct 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ekaterina Bobrovnikova-MarjonJ Alan Diehl
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Sep 1, 2009·Chemistry & Biology·Shinji KamisukiMotonari Uesugi
Sep 2, 2010·Journal of Lipid Research·Jenson QiMargery A Connelly
Dec 14, 2011·Trends in Endocrinology and Metabolism : TEM·Tae-Il Jeon, Timothy F Osborne
Sep 27, 2012·Cancer Discovery·Jason R Cantor, David M Sabatini
Nov 6, 2013·Biochemical and Biophysical Research Communications·Dietlind SommerweissWieland Kiess
Nov 10, 2013·Disease Models & Mechanisms·Franziska BaenkeAlmut Schulze
Jan 19, 2016·Trends in Biochemical Sciences·Maria V Liberti, Jason W Locasale
Jan 26, 2016·Oncogenesis·S Beloribi-DjefafliaF Guillaumond
Feb 18, 2016·The FEBS Journal·Barrie Peck, Almut Schulze
Jun 22, 2016·Journal of Lipid Research·Wei ShaoPeter J Espenshade
Jul 6, 2016·The Journal of Biological Chemistry·Ankur A GholkarJorge Z Torres
Jul 19, 2016·ACS Chemical Biology·Nasi LiG Ekin Atilla-Gokcumen
Mar 30, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jingquan HeGuangwei Du
May 10, 2017·Biochemical and Biophysical Research Communications· SiqingaowaChangiz Taghibiglou
Dec 1, 2017·Biochemistry·Nasi LiG Ekin Atilla-Gokcumen
Jan 18, 2018·Nature Genetics·Ming ChenPier Paolo Pandolfi

❮ Previous
Next ❯

Citations

Sep 15, 2020·Drug Design, Development and Therapy·Ying LiuQifeng Yang
Sep 26, 2020·Frontiers in Oncology·Linyuan XueXiangyan Li
Dec 29, 2020·Molecular and Cellular Endocrinology·Qiong WangJie Zhou
Jan 9, 2021·Frontiers in Oncology·Anna Mukha, Anna Dubrovska
Dec 8, 2020·Trends in Cancer·Marina BacciAndrea Morandi
Apr 30, 2020·Molecular Therapy. Methods & Clinical Development·Dhara ShahVinay Kumar Aakalu
Jul 28, 2020·Advanced Drug Delivery Reviews·Lisa M ButlerJohannes V Swinnen
Apr 24, 2021·Journal of Pharmaceutical and Biomedical Analysis·Jing YuHonghao Zhou
May 18, 2019·Proteomics·Nasi LiGunes Ekin Atilla-Gokcumen
Jun 11, 2021·Frontiers in Oncology·Isabella GiacominiVeronica Cocetta
Nov 16, 2021·Lipids in Health and Disease·Do-Won JeongYang-Sook Chun

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
xenografts
Assay
Profiler

Software Mentioned

Mass Profiler Professional (
MassHunter Profinder
ImageJ
MassHunter Qualitative Analysis ( Agilent
GraphPad Prism
Profinder

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.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.