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

Liu, Jing; Yang, Yanfang; Wang, Hongwei; Wang, Bin; Zhao, Kaili; Jiang, Wenna; Bai, Weiwei; Li, Jun; Yin, Jian

doi:10.1007/s10549-018-4833-8

Cited by 27 publications

(23 citation statements)

References 32 publications

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“…Another study has shown that syntenin1 is highly expressed in TNBC tissues and increases the expression level of PD-L1 by activating STAT3, consequently attenuates the response of TNBC to anti-PD-L1 treatment [74]. Moreover, direct inhibition of STAT3 overcomes the resistance of TNBC to immunotherapies, which confirms its immunosuppressive activity [72, 74].…”

Section: The Stat3 Signaling Pathway In Triple Negative Breast Cancermentioning

confidence: 99%

“…The mechanism studies have shown that pSTAT1 and pSTAT3 form heterodimers in the cytoplasm and translocate into the nucleus, where the pSTAT1-pSTAT3 dimers bind to the PD-L1 promoter and activate its transcription [72]. Another study has shown that syntenin1 is highly expressed in TNBC tissues and increases the expression level of PD-L1 by activating STAT3, consequently attenuates the response of TNBC to anti-PD-L1 treatment [74]. Moreover, direct inhibition of STAT3 overcomes the resistance of TNBC to immunotherapies, which confirms its immunosuppressive activity [72, 74].…”

Section: The Stat3 Signaling Pathway In Triple Negative Breast Cancermentioning

confidence: 99%

See 1 more Smart Citation

STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

Qin

Li²,

Zhang³

et al. 2019

J Exp Clin Cancer Res

284

187

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Triple negative breast cancer (TNBC), which is typically lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), represents the most aggressive and mortal subtype of breast cancer. Currently, only a few treatment options are available for TNBC due to the absence of molecular targets, which underscores the need for developing novel therapeutic and preventive approaches for this disease. Recent evidence from clinical trials and preclinical studies has demonstrated a pivotal role of signal transducer and activator of transcription 3 (STAT3) in the initiation, progression, metastasis, and immune evasion of TNBC. STAT3 is overexpressed and constitutively activated in TNBC cells and contributes to cell survival, proliferation, cell cycle progression, anti-apoptosis, migration, invasion, angiogenesis, chemoresistance, immunosuppression, and stem cells self-renewal and differentiation by regulating the expression of its downstream target genes. STAT3 small molecule inhibitors have been developed and shown excellent anticancer activities in in vitro and in vivo models of TNBC. This review discusses the recent advances in the understanding of STAT3, with a focus on STAT3's oncogenic role in TNBC. The current targeting strategies and representative small molecule inhibitors of STAT3 are highlighted. We also propose potential strategies that can be further examined for developing more specific and effective inhibitors for TNBC prevention and therapy.

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Section: The Stat3 Signaling Pathway In Triple Negative Breast Cancermentioning

confidence: 99%

Section: The Stat3 Signaling Pathway In Triple Negative Breast Cancermentioning

confidence: 99%

STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

Qin

Li²,

Zhang³

et al. 2019

J Exp Clin Cancer Res

284

187

View full text Add to dashboard Cite

show abstract

“…Anti-CTLA-4 treatment reduces the activation threshold of T cells and magnifies the tumor-specific immune response [89, 90]. Some studies revealed that anti-CTLA-4 mAb could selectively eradicate Tregs by antibody-dependent cell-mediated cytotoxicity (ADCC) effect [91, 92].…”

Section: Introductionmentioning

confidence: 99%

Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy

et al. 2019

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During tumor progression, a subset of cancer cells escape from immune surveillance and eventually develop into measurable tumor mass. Cancer immunotherapy eradicates tumor cells by enhancing multiple steps in cancer-immunity cycle including antigen presentation, T cell priming, activation, and immune killing activity. Immunotherapy has been verified as an effective strategy in multiple cancers, but some problems still exist in actual clinical practice such as frequent primary and adaptive resistance. Combination with other adjuvant therapies gives us a new perspective to overcome the emerging obstacles in immunotherapy application. Recently, a series of studies demonstrated that the vital component of host innate immunity — cGAS-STING pathway might play an important role in anti-cancer immunity. It is generally acknowledged that the downstream signals of cGAS-STING especially type I interferon (IFN) bridge innate immunity and adaptive immunity. Given the functions of type I IFN in promoting the maturation and migration of dendritic cells, enhancing cytotoxic T lymphocyte- or natural killer cell-mediated cytotoxicity effect, and protecting effector cells from apoptosis, we believe cGAS-STING agonist might be used as sensitizer for multiple immunotherapies such as cancer vaccine, immune checkpoint blockade, and chimeric antigen receptor T cell therapy. In this review, we highlight the latest understanding of cGAS-STING pathway and the advances of the combination therapy of STING agonist and immunotherapy.

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“…SDCBP (also known as Syntenin) is a PDZ domain scaffolding protein that binds Syndecan (Grootjans et al 1997) and regulates exosome formation (Baietti et al 2012). SDCBP has been associated with worse breast cancer outcome that has been attributed to multiple mechanisms, including tumor cell proliferation, invasiveness, and evasion of the antitumor immunity (Liu et al 2018; Yang et al 2013; Qian et al 2013; Koo et al 2002). To our knowledge, this study is the first to link SDCBP with a potential role in breast cancer incidence, which is supported by its close proximity to the rs4305889 [G] risk allele (Kuchenbaecker et al 2014).…”

Section: Resultsmentioning

confidence: 99%

Identification of a Rat Mammary Tumor Risk Locus That Is Syntenic with the Commonly Amplified 8q12.1 and 8q22.1 Regions in Human Breast Cancer Patients

Tsaih

Lemke

Schilling

et al. 2019

G3 Genes|Genomes|Genetics

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Breast cancer risk is 31% heritable, yet the majority of the underlying risk factors remain poorly defined. Here, we used F2-linkage analysis in a rat mammary tumor model to identify a novel 11.2 Mb modifier locus of tumor incidence and burden on rat chromosome 5 (chr5: 15.4 – 26.6 Mb). Genomic and RNA sequencing analysis identified four differentially expressed candidates: TMEM68 , IMPAD1 , SDCBP , and RBM12B . Analysis of the human syntenic candidate region revealed that SDCBP is in close proximity to a previously reported genetic risk locus for human breast cancer. Moreover, analysis of the candidate genes in The Cancer Genome Atlas (TCGA) revealed that they fall within the commonly amplified 8q12.1 and 8q22.1 regions in human breast cancer patients and are correlated with worse overall survival. Collectively, this study presents novel evidence suggesting that TMEM68 , IMPAD1 , SDCBP , and RBM12B are potential modifiers of human breast cancer risk and outcome.

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

Cited by 27 publications

References 32 publications

STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy

Identification of a Rat Mammary Tumor Risk Locus That Is Syntenic with the Commonly Amplified 8q12.1 and 8q22.1 Regions in Human Breast Cancer Patients

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