Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is receptor tyrosine-protein kinase (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine and phosphatidylethanolamine; their changes on membrane composition occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35-40% of ERBB2-positive breast cancers. In this study, we demonstrate that ethanol administration promotes STARD10 and ERBB2 expression that is significantly associated with increased cell malignancy and aggressiveness. Consistently, ERBB2 overexpression causes an increase in STARD10 expression, while overexpression of ERBB2’s downstream targets, p65, c-MYC, c-FOS or c-JUN induces STARD10 promoter activity, correlative of enhanced ERBB2 function STARD10-mediated cellular membrane fluidity and intracellular calcium concentration impacts ERBB2 signaling pathway as evaluated by enhancedp65 nuclear translocation and binding to both ERBB2 and STARD10 promoters. Basically, we proved that STARD10 and ERBB2 positively regulate each other’s expression and function. Taken together, our data demonstrate that ethanol can modulate ERBB2’s function in breast cancer via a novel interplay with STARD10.
|Titolo:||Star-related lipid transfer protein 10 (STARD10): a novel key player in alcohol-induced breast cancer progression|
|Data di pubblicazione:||6-feb-2019|
|Tipologia:||8.1 Tesi di Dottorato|