Dependence of ABCB1 transporter expression and function on distinct sphingolipids generated by ceramide synthases-2 and -6 in chemoresistant renal cancer.
ATP Binding Cassette Transporter, Subfamily B
/ biosynthesis
Ceramides
/ metabolism
Doxorubicin
/ pharmacology
Drug Resistance, Neoplasm
Endoplasmic Reticulum-Associated Degradation
Female
Humans
Kidney Neoplasms
/ drug therapy
Male
Membrane Proteins
/ metabolism
RNA, Messenger
/ genetics
Sphingolipids
/ metabolism
Sphingosine N-Acyltransferase
/ genetics
Tandem Mass Spectrometry
Tumor Microenvironment
Tumor Suppressor Proteins
ABC transporter
P-glycoprotein
cancer drug resistance
sphingolipids
unfolded protein response
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
01
12
2021
accepted:
07
12
2021
pubmed:
17
12
2021
medline:
29
4
2022
entrez:
16
12
2021
Statut:
ppublish
Résumé
Oncogenic multidrug resistance is commonly intrinsic to renal cancer based on the physiological expression of detoxification transporters, particularly ABCB1, thus hampering chemotherapy. ABCB1 activity is directly dependent on its lipid microenvironment, localizing to cholesterol- and sphingomyelin (SM)-rich domains. As ceramides are the sole source for SMs, we hypothesized that ceramide synthase (CerS)-derived ceramides regulate ABCB1 activity. Using data from RNA-Seq databases, we found that patient kidney tumors exhibited increased CerS2 mRNA, which was inversely correlated with CerS6 mRNA in ABCB1
Identifiants
pubmed: 34915026
pii: S0021-9258(21)01302-8
doi: 10.1016/j.jbc.2021.101492
pmc: PMC8804196
pii:
doi:
Substances chimiques
ABCB1 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
Ceramides
0
Membrane Proteins
0
RNA, Messenger
0
Sphingolipids
0
Tumor Suppressor Proteins
0
Doxorubicin
80168379AG
CERS2 protein, human
EC 2.3.1.24
CERS6 protein, human
EC 2.3.1.24
Sphingosine N-Acyltransferase
EC 2.3.1.24
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101492Subventions
Organisme : NCI NIH HHS
ID : R01 CA173687
Pays : United States
Organisme : NCRR NIH HHS
ID : C06 RR015455
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103339
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE016572
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA138313
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA203628
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.