title: Annexin-A1 controls an ERK-RhoA-NFκB activation loop in breast cancer cells.
abstract: Wound healing is critical for normal development and pathological processes including cancer cell metastasis. MAPK, Rho-GTPases and NFκB 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 NFκB. 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-κB activation, where constitutively active RhoA potentiates NFκB activation, while dominant negative RhoA inhibits NFκB 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 NFκB, ERK1/2 and RhoA.
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors: Pradeep
authors: P
authors: Bist
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors: Qian Hui
authors: QH
authors: Phua
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors: Shinla
authors: S
authors: Shu
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors: Yuan
authors: Y
authors: Yi
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors: Durkeshwari
authors: D
authors: Anbalagan
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors: Lay Hoon
authors: LH
authors: Lee
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore.
authors: Gautam
authors: G
authors: Sethi
authors: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors: Boon Chuan
authors: BC
authors: Low
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore. Electronic address: linalim@nus.edu.sg.
authors: Lina H K
authors: LH
authors: Lim
mesh_terms: D017305:Annexin A1 / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D017305:Annexin A1; D016328:NF-kappa B; C066737:RHOA protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D020742:rhoA GTP-Binding Protein
keywords: Annexin-1 (ANXA1); ERK; Metastasis; Nuclear factor-kappa B (NF-κB); RhoA; Stress fibers