Trefoil Factor-1 (TFF1) Enhances Oncogenicity of Mammary Carcinoma Cells

Author:

Amiry Naeem1,Kong Xiangjun2,Muniraj Nethaji1,Kannan Nagarajan1,Grandison Prudence M.1,Lin Juan2,Yang Yulu2,Vouyovitch Cécile M.3,Borges Sahra3,Perry Jo K.1,Mertani Hichem C.3,Zhu Tao2,Liu Dongxu1,Lobie Peter E.14

Affiliation:

1. Liggins Institute (N.A., N.M., N.K., P.M.G., J.K.P., D.L., P.E.L.), University of Auckland, Private Bag 92019, Auckland 1023, New Zealand

2. Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences (X.K., J.L., Y.Y., T.Z.), University of Science and Technology of China, Hefei, Anhui 230027, People’s Republic of China

3. Centre National de la Recherche Scientifique (C.M.V., S.B., H.C.M.), Unité Mixte de Recherche 5123, Physiologie Moléculaire, Université Claude Bernard Lyon I, Université de Lyon, 69622 Villeurbanne Cedex, France

4. Department of Molecular Medicine and Pathology (P.E.L.), Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1023, New Zealand

Abstract

Abstract The functional role of autocrine trefoil factor-1 (TFF1) in mammary carcinoma has not been previously elucidated. Herein, we demonstrate that forced expression of TFF1 in mammary carcinoma cells resulted in increased total cell number as a consequence of increased cell proliferation and survival. Forced expression of TFF1 enhanced anchorage-independent growth and promoted scattered cell morphology with increased cell migration and invasion. Moreover, forced expression of TFF1 increased tumor size in xenograft models. Conversely, RNA interference-mediated depletion of TFF1 in mammary carcinoma cells significantly reduced anchorage-independent growth and migration. Furthermore, neutralization of secreted TFF1 protein by polyclonal antibody decreased mammary carcinoma cell viability in vitro and resulted in regression of mammary carcinoma xenografts. We have therefore demonstrated that TFF1 possesses oncogenic functions in mammary carcinoma cells. Functional antagonism of TFF1 can therefore be considered as a novel therapeutic strategy for mammary carcinoma.

Publisher

The Endocrine Society

Subject

Endocrinology

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