Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells.
LC3C
exocytosis
lysosome
renal cancer
zinc
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:
05 2023
05 2023
Historique:
received:
22
10
2022
revised:
14
03
2023
accepted:
22
03
2023
medline:
29
5
2023
pubmed:
2
4
2023
entrez:
1
4
2023
Statut:
ppublish
Résumé
Microtubule-associated protein 1 light chain 3 gamma (MAP1LC3C or LC3C) is a member of the microtubule-associated family of proteins that are essential in the formation of autophagosomes and lysosomal degradation of cargo. LC3C has tumor-suppressing activity, and its expression is dependent on kidney cancer tumor suppressors, such as von Hippel-Lindau protein and folliculin. Recently, we demonstrated that LC3C autophagy is regulated by noncanonical upstream regulatory complexes and targets for degradation postdivision midbody rings associated with cancer cell stemness. Here, we show that loss of LC3C leads to peripheral positioning of the lysosomes and lysosomal exocytosis (LE). This process is independent of the autophagic activity of LC3C. Analysis of isogenic cells with low and high LE shows substantial transcriptomic reprogramming with altered expression of zinc (Zn)-related genes and activity of polycomb repressor complex 2, accompanied by a robust decrease in intracellular Zn. In addition, metabolomic analysis revealed alterations in amino acid steady-state levels. Cells with augmented LE show increased tumor initiation properties and form aggressive tumors in xenograft models. Immunocytochemistry identified high levels of lysosomal-associated membrane protein 1 on the plasma membrane of cancer cells in human clear cell renal cell carcinoma and reduced levels of Zn, suggesting that LE occurs in clear cell renal cell carcinoma, potentially contributing to the loss of Zn. These data indicate that the reprogramming of lysosomal localization and Zn metabolism with implication for epigenetic remodeling in a subpopulation of tumor-propagating cancer cells is an important aspect of tumor-suppressing activity of LC3C.
Identifiants
pubmed: 37003503
pii: S0021-9258(23)00305-8
doi: 10.1016/j.jbc.2023.104663
pmc: PMC10173779
pii:
doi:
Substances chimiques
MAP1LC3C protein, human
0
Microtubule-Associated Proteins
0
Zinc
J41CSQ7QDS
Polycomb Repressive Complex 2
EC 2.1.1.43
LAMP1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
104663Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM128216
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES006096
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA168815
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA117846
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they do not have conflicts of interests with the content of this article.