Isthmin-1 promotes growth and progression of colorectal cancer through the interaction with EGFR and YBX-1.
Cancer Lett
; 590: 216868, 2024 May 28.
Article
in En
| MEDLINE
| ID: mdl-38593920
ABSTRACT
While previous studies have indicated the involvement of Isthmin 1 (ISM1), a secreted protein, in cancer development, the precise mechanisms have remained elusive. In this study, we unveiled that ISM1 is significantly overexpressed in both the blood and tissue samples of colorectal cancer (CRC) patients, correlating with their poor prognosis. Functional experiments demonstrated that enforced ISM1 expression significantly enhances CRC proliferation, migration, invasion and tumor growth. Notably, our investigation reveals an interaction of ISM1 with epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase (RTK) family of CRC cells. The binding of ISM1 triggered EGFR activation and initiate downstream signaling pathways. Meanwhile, intracellular ISM1 interacted with Y-box binding protein 1 (YBX1), enhancing its transcriptional regulation on EGFR. Furthermore, our research uncovered the regulation of ISM1 expression by the hypoxia-inducible transcription factor HIF-1α in CRC cells. Mechanistically, we identified HIF-1α as a direct regulator of ISM1, binding to a hypoxia response element on its promoter. This novel mechanism illuminated potential therapeutic targets, offering insights into restraining HIF-1α/ISM1/EGFR-driven CRC progression and metastasis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Disease Progression
/
Cell Proliferation
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
Y-Box-Binding Protein 1
/
ErbB Receptors
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Cancer Lett
Year:
2024
Type:
Article
Affiliation country:
China