Type IV collagen α5 chain promotes luminal breast cancer progression through c-Myc-driven glycolysis.
COL4A5
Myc
basement membrane
glycolysis
luminal breast cancer
type IV collagen
Journal
Journal of molecular cell biology
ISSN: 1759-4685
Titre abrégé: J Mol Cell Biol
Pays: United States
ID NLM: 101503669
Informations de publication
Date de publication:
29 03 2023
29 03 2023
Historique:
accepted:
07
12
2022
received:
28
05
2022
revised:
27
09
2022
medline:
7
4
2023
pubmed:
10
12
2022
entrez:
9
12
2022
Statut:
ppublish
Résumé
Cancer cell metabolism reprogramming is one of the hallmarks of cancer. Cancer cells preferentially utilize aerobic glycolysis, which is regulated by activated oncogenes and the tumor microenvironment. Extracellular matrix (ECM) in the tumor microenvironment, including the basement membranes (BMs), is dynamically remodeled. However, whether and how ECM regulates tumor glycolysis is largely unknown. We show that type IV collagens, components of BMs essential for the tissue integrity and proper function, are differentially expressed in breast cancer subtypes that α5 chain (α5(IV)) is preferentially expressed in the luminal-type breast cancer and is regulated by estrogen receptor-α. α5(IV) is indispensable for luminal breast cancer development. Ablation of α5(IV) significantly reduces the growth of luminal-type breast cancer cells and impedes the development of luminal-type breast cancer. Impaired cell growth and tumor development capability of α5(IV)-ablated luminal breast cancer cells is attributed to the reduced expression of glucose transporter and glycolytic enzymes and impaired glycolysis in luminal breast cancer cells. Non-integrin collagen receptor discoidin domain receptor-1 (DDR1) expression and p38 mitogen-activated protein kinase activation are attenuated in α5(IV)-ablated luminal breast cancer cells, resulting in reduced c-Myc oncogene expression and phosphorylation. Ectopic expression of constitutively active DDR1 or c-Myc restores the expression of glucose transporter and glycolytic enzymes, and thereafter restores aerobic glycolysis, cell proliferation, and tumor growth of luminal breast cancer. Thus, type IV collagen α5 chain is a luminal-type breast cancer-specific microenvironmental regulator modulating cancer cell metabolism.
Identifiants
pubmed: 36484686
pii: 6885458
doi: 10.1093/jmcb/mjac068
pmc: PMC10077331
pii:
doi:
Substances chimiques
Collagen Type IV
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.
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