The Aryl Hydrocarbon Receptor Undergoes Chaperone-Mediated Autophagy in Triple-Negative Breast Cancer Cells.
Int J Mol Sci
; 22(4)2021 Feb 06.
Article
in En
| MEDLINE
| ID: mdl-33562118
ABSTRACT
The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule expressed in many cell types, including triple-negative and non-triple-negative breast cancer cells. It affects breast cancer growth and crosstalk with estrogen receptor signaling. Normally, this receptor is degraded shortly after ligand activation via the 26S proteasome. Here, we report that AHR undergoes chaperone-mediated autophagy in MDA-MB-468 triple-negative breast cancer cells. This lysosomal degradation of AHR exhibits the following characteristics (1) it is triggered by 6 amino-nicotinamide, starvation, and piperazinylpyrimidine compound Q18; (2) it is not observed in non-triple-negative breast cancer cells (MCF-7, T47D, and MDA-MB-361); (3) it can be inhibited by progesterone receptor B but not estrogen receptor alpha; (4) it can be reversed by chloroquine but not MG132; (5) it requires LAMP2A; and (6) it involves AHR-HSC70 and AHR-LAMP2A interactions. The NEKFF sequence localized at amino acid 558 of human AHR appears to be a KFERQ-like motif of chaperone-mediated autophagy, responsible for the LAMP2A-mediated AHR protein degradation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Aryl Hydrocarbon
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Basic Helix-Loop-Helix Transcription Factors
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Lysosomal-Associated Membrane Protein 2
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Proteolysis
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Triple Negative Breast Neoplasms
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Chaperone-Mediated Autophagy
Limits:
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2021
Document type:
Article
Affiliation country: