Deubiquitinase USP9x regulates the proline biosynthesis pathway in non-small cell lung cancer.
Cell Death Discov
; 10(1): 342, 2024 Jul 29.
Article
in En
| MEDLINE
| ID: mdl-39075050
ABSTRACT
Metabolic rewiring has been recognized as a hallmark of malignant transformation, supplying the biosynthetic and energetic demands for rapid cancer cell proliferation and tumor progression. A comprehensive understanding of the regulatory mechanisms governing these metabolic processes is still limited. Here, we identify the deubiquitinase ubiquitin-specific peptidase 9 X-linked (USP9x) as a positive regulator of the proline biosynthesis pathway in non-small cell lung cancer (NSCLC). Our findings demonstrate USP9x directly stabilizes pyrroline-5-carboxylate reductase 3 (PYCR3), a key enzyme in the proline cycle. Disruption of proline biosynthesis by either USP9x or PYCR3 knockdown influences the proline cycle leading to a decreased activity of the connected pentose phosphate pathway and mitochondrial respiration. We show that USP9x is elevated in human cancer tissues and its suppression impairs NSCLC growth in vitro and in vivo. Overall, our study uncovers a novel function of USP9x as a regulator of the proline biosynthesis pathway, which impacts lung cancer growth and progression, and implicates a new potential therapeutic avenue.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Cell Death Discov
Year:
2024
Document type:
Article
Affiliation country:
Sweden
Country of publication:
United States