Betacellulin enhances ovarian cancer cell migration by up-regulating Connexin43 via MEK-ERK signaling.

Betacellulin enhances ovarian cancer cell migration by up-regulating Connexin43 via MEK-ERK signaling. Cell Signal. 2019 Oct 22;:109439 Authors: Zhao J, Klausen C, Yi Y, Cheng JC, Chang HM, Leung PCK Abstract Epithelial ovarian cancer is the fifth common cause of cancer death in women and the most lethal gynecological malignancies. Our previous studies have shown that up-regulation of Connexin43, a gap-junction subunit crucial for cell-cell communication, enhances ovarian cancer cell migration. Betacellulin is a member of the epidermal growth factor (EGF) family which can bind to multiple EGF family receptors. Overexpression of betacellulin is found in a variety of cancers and is associated with reduced survival. However, the specific roles and molecular mechanisms of betacellulin in ovarian cancer progression are poorly understood. In the current study, we tested the hypothesis that betacellulin induces ovarian cancer cell migration by up-regulating Connexin43. Our results showed that treatment with betacellulin significantly increased Connexin43 expression and cell migration in both OVCAR4 and SKOV3 ovarian cancer cell lines. Moreover, betacellulin induced the activation of MEK-ERK signaling, and its effects on Connexin43 were inhibited by pre-treatment with U0126. Pre-treatment with AG1478 totally blocked the activation of MEK-ERK signaling but only partially inhibited betacellulin-induced Connexin43 expression and cell migration....
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research