title: Loss of Dab2 expression in breast cancer cells impairs their ability to deplete TGF-β and induce Tregs development via TGF-β.
abstract: Dab2 is a multifunctional adapter protein which is frequently under-expressed in a variety of cancers. It is implicated in many critical functions, including several signaling pathways, cell arrangement, differentiation of stem cells, and receptor endocytosis. Transforming growth factor-β (TGF-β) is a secreted multifunctional protein that controls several developmental processes and pathogenesis of many diseases. It has been documented that Dab2 played an important role in TGF-β receptors endocytosis. Here, we present evidence that re-expression of Dab2 in SK-BR-3 cell partially restored its ability to deplete TGF-β in surrounding medium by normalizing the trafficking of TGF-β receptors. We also demonstrate that the difference in TGF-β depletions produced by Dab2 expression was sufficient to impact on the conversion of naive CD4+ T cells to regulatory T cells (Tregs), and thus inhibited the proliferation of T cells. This work revealed a critical result that breast cancer cell was deficient in Dab2 expression and related receptor endocytosis-mediated TGF-β depletion, which may contribute to the accumulation of TGF-β in tumor microenvironment and the induction of immune tolerance.
authors.affiliation: Department of Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P. R. China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P. R. China.
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P. R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000209:etiology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins