Annexin-A1 controls an ERK-RhoA-NFκB activation loop in breast cancer cells

Wound healing is critical for normal development and pathological processes including cancer cell metastasis. MAPK, Rho-GTPases and NF kappa B are important regulators of wound healing, but mechanisms for their integration are incompletely understood. Annexin-A1 (ANXA1) is upregulated in invasive breast cancer cells resulting in constitutive activation of NF kappa B. We show here that silencing ANXA1 increases the formation of stress fibers and focal adhesions, which may inhibit wound healing. ANXA1 regulated wound healing is dependent on the activation of ERK1/2. ANXA1 increases the activation of RhoA, which is dependent on ERK activation. Furthermore, active RhoA is important in NF-kappa B activation, where constitutively active RhoA potentiates NF kappa B activation, while dominant negative RhoA inhibits NF kappa B activation in response to CXCL12 stimulation and active MEKK plasmids. These findings establish a central role for ANXA1 in the cell migration through the activation of NF kappa B, ERK1/2 and RhoA. (C) 2015 Elsevier Inc. All rights reserved.