The motility of breast cancer cells is stimulated by HMGB1/RAGE interaction but the truncated form lacking the C terminus has no effect

Autor: Todorova, Jordana, Myashkova, Shazie, Petrova, Maria, Gospodinov, Anastas, Pasheva, Evdokia
Rok vydání: 2022
Předmět:
Zdroj: BioDiscovery 24: e93641
ISSN: 2050-2966
DOI: 10.3897/biodiscovery.24.e93641
Popis: HMGB1/RAGE is identified as a ligand-receptor pair that plays an important role in tumorogenesis. HMGB1 and RAGE levels are higher in most human tumors and their overexpression is associated with tumor progression. The causes of breast cancer are still poorly understood. One reason might be the existence of subtypes within various cellular mechanisms as hormone-dependent and hormone -independent malignant processes. We investigated the effect of HMGB1 protein and its truncated form lacking the C terminus on the RAGE expression and cell motility of breast cancer cell lines; MCF7-noninvasive, MDA-MB-231-invasive and normal breast epithelial one MCF10. The results demonstrate that the effects of HMGB1 and HMGB1∆C through RAGE association are observed exclusively for the hormone independent MDA-MB-231 cell line. The mobility of MDA-MB-231 cells was stimulated only by the full length HMGB1. Our results suggest that HMGB1/RAGE signaling should be considered as an essential process for the development of hormone independent breast cancers with great invasive potential. The truncated form plays the role of a blocking molecule that ”locks” the receptor and inactivates it. This makes the tailless molecule a promising therapeutic agent that competes for the biologically active HMGB1 ligand and prevents the downstream signaling through RAGE.
Databáze: OpenAIRE