Syntenin1/MDA-9 (SDCBP) induces immune evasion in triple-negative breast cancer by upregulating PD-L1

Breast Cancer Research and Treatment
Jing LiuJian Yin

Abstract

Syntenin1/SDCBP (syndecan binding protein), also known as melanoma differentiation associated gene-9 (MDA-9), is a PDZ domain-containing molecule, which was initially identified as a key oncogene in melanoma. However, the role of syntenin1 in triple-negative breast cancer (TNBC), especially in suppression of antitumour immune response, remains unknown. One hundred TNBC tissues were obtained after radical resection and used for analysis. High syntenin1 expression was associated with increased tumour size (r = 0.421, P < 0.001), presence of lymph node metastasis (r = 0.221, P = 0.044) and poor overall survival (P = 0.01) and recurrence-free survival (P = 0.007). Syntenin1 overexpression significantly promoted 4T1 tumour growth and lung metastasis in BALB/c mice by affecting CD8+ T cells. Western blot and flow cytometry analyses demonstrated that syntenin1 induced CD8+ T cell apoptosis in vitro and in vivo through upregulating PD-L1. Western blot demonstrated that syntenin1 upregulated PD-L1 expression by inducing Tyr705 stat3 phosphorylation, which was further confirmed by stat3 inhibition study. The correlation between syntenin1 and PD-L1 was further confirmed using tumour tissues derived from patients with TNBC (r = 0.509, P < ...Continue Reading

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Citations

May 16, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jiang-Jiang QinWei-Dong Zhang
Apr 3, 2019·Journal of Hematology & Oncology·Anping LiKongming Wu
Dec 31, 2019·Seminars in Cancer Biology·Semir VranicJuan Palazzo
May 22, 2021·Proceedings of the National Academy of Sciences of the United States of America·Anjan K PradhanPaul B Fisher
Jun 19, 2021·Frontiers in Oncology·Alyssa S ZembroskiDorothy Teegarden

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