PMID- 34514415
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220831
IS  - 2632-8674 (Electronic)
IS  - 2632-8674 (Linking)
VI  - 3
IP  - 3
DP  - 2021 Sep
TI  - CPT1A and fatty acid beta-oxidation are essential for tumor cell growth and survival 
      in hormone receptor-positive breast cancer.
PG  - zcab035
LID - 10.1093/narcan/zcab035 [doi]
LID - zcab035
AB  - Chromosome 11q13-14 amplification is a defining feature of high-risk hormone 
      receptor-positive (HR+) breast cancer; however, the mechanism(s) by which this 
      amplicon contributes to breast tumorigenesis remains unclear. In the current 
      study, proteogenomic analyses of >3000 breast tumors from the TCGA, METABRIC and 
      CPTAC studies demonstrated that carnitine palmitoyltransferase 1A (CPT1A), which 
      is localized to this amplicon, is overexpressed at the mRNA and protein level in 
      aggressive luminal tumors, strongly associated with indicators of tumor 
      proliferation and a predictor of poor prognosis. In vitro genetic studies 
      demonstrated that CPT1A is required for and can promote luminal breast cancer 
      proliferation, survival, as well as colony and mammosphere formation. Since CPT1A 
      is the rate-limiting enzyme during fatty acid oxidation (FAO), our data indicate 
      that FAO may be essential for these tumors. Pharmacologic inhibition of FAO 
      prevented in vitro and in vivo tumor growth and cell proliferation as well as 
      promoted apoptosis in luminal breast cancer cells and orthotopic xenograft tumor 
      models. Collectively, our data establish an oncogenic role for CPT1A and FAO in 
      HR+ luminal tumors and provide preclinical evidence and rationale supporting 
      further investigation of FAO as a potential therapeutic opportunity for the 
      treatment of HR+ breast cancer.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of NAR 
      Cancer.
FAU - Jariwala, Nidhi
AU  - Jariwala N
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
FAU - Mehta, Gaurav A
AU  - Mehta GA
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
FAU - Bhatt, Vrushank
AU  - Bhatt V
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
FAU - Hussein, Shaimaa
AU  - Hussein S
AUID- ORCID: 0000-0003-0849-9670
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
FAU - Parker, Kimberly A
AU  - Parker KA
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
FAU - Yunus, Neha
AU  - Yunus N
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
FAU - Parker, Joel S
AU  - Parker JS
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill, Chapel Hill NC, 27599, USA.
FAU - Guo, Jessie Yanxiang
AU  - Guo JY
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
FAU - Gatza, Michael L
AU  - Gatza ML
AUID- ORCID: 0000-0001-6796-7791
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
LA  - eng
GR  - P30 CA072720/CA/NCI NIH HHS/United States
GR  - R01 CA237347/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20210909
PL  - England
TA  - NAR Cancer
JT  - NAR cancer
JID - 101769553
PMC - PMC8428294
EDAT- 2021/09/14 06:00
MHDA- 2021/09/14 06:01
PMCR- 2021/09/09
CRDT- 2021/09/13 07:03
PHST- 2021/04/29 00:00 [received]
PHST- 2021/08/18 00:00 [revised]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/09/13 07:03 [entrez]
PHST- 2021/09/14 06:00 [pubmed]
PHST- 2021/09/14 06:01 [medline]
PHST- 2021/09/09 00:00 [pmc-release]
AID - zcab035 [pii]
AID - 10.1093/narcan/zcab035 [doi]
PST - epublish
SO  - NAR Cancer. 2021 Sep 9;3(3):zcab035. doi: 10.1093/narcan/zcab035. eCollection 
      2021 Sep.