Bcl-3 regulates TGFβ signaling by stabilizing Smad3 during breast cancer pulmonary metastasis

Chen, Xi; Cao, Xinwei; Sun, Xiaohua; Rong, Lei; Chen, Pengfei; Zhao, Yongxu; Jiang, Yuhang; Yin, Jie; Chen, Ran; Ye, Deji; Wang, Qi; Liu, Zhanjie; Liu, Sanhong; Cheng, Cheng; Mao, Jie; Hou, Yingyong; Wang, Mingliang; Siebenlist, Ulrich; Chin, Yvette; Wang, Ying; Cao, Liu; Hu, Guohong; Zhang, Xiaoren

doi:10.1038/cddis.2016.405

Cited by 41 publications

(46 citation statements)

References 46 publications

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“…Serial sections of formalin-fixed, paraffin-embedded tissues from 60 patients were obtained between September 2014 and March 2017. The routine immunohistochemistry were performed as previously described 25 . Slices were immunostained using anti-ACSS3 (Invitrogen, PA5-80305) antibody.…”

Section: Clinical Samples and Immunohistochemistrymentioning

confidence: 99%

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

et al. 2020

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Cancer cells adapt to nutrient-deprived tumor microenvironment during progression via regulating the level and function of metabolic enzymes. Acetyl-coenzyme A (AcCoA) is a key metabolic intermediate that is crucial for cancer cell metabolism, especially under metabolic stress. It is of special significance to decipher the role acetyl-CoA synthetase short chain family (ACSS) in cancer cells confronting metabolic stress. Here we analyzed the generation of lipogenic AcCoA in bladder cancer cells under metabolic stress and found that in bladder urothelial carcinoma (BLCA) cells, the proportion of lipogenic AcCoA generated from glucose were largely reduced under metabolic stress. Our results revealed that ACSS3 was responsible for lipogenic AcCoA synthesis in BLCA cells under metabolic stress. Interestingly, we found that ACSS3 was required for acetate utilization and histone acetylation. Moreover, our data illustrated that ACSS3 promoted BLCA cell growth. In addition, through analyzing clinical samples, we found that both mRNA and protein levels of ACSS3 were dramatically upregulated in BLCA samples in comparison with adjacent controls and BLCA patients with lower ACSS3 expression were entitled with longer overall survival. Our data revealed an oncogenic role of ACSS3 via regulating AcCoA generation in BLCA and provided a promising target in metabolic pathway for BLCA treatment.

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Section: Clinical Samples and Immunohistochemistrymentioning

confidence: 99%

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

et al. 2020

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“…The link between Bcl3 overexpression and malignant transformation was suggested to stem from its transcriptional up-regulation of cyclin D1 (57), increased expression of HDM2, the main negative regulator of p53 (58), and regulation of DNA damage response (59). In addition, recent studies have shown that Bcl3 induces expression of proinflammatory cytokines IL-8 and IL-17 in cutaneous T cell lymphoma cells (16), and TGF␤ signaling in breast cancer (60). Our present findings demonstrate that Bcl3 promotes expression of PD-L1, indicating that in addition to regulating NF-Bdependent genes involved in cell survival and proliferation, Bcl3 controls genes involved in immune escape.…”

Section: Bcl3 Induces Pd-l1 In Ovarian Cancer Cellsmentioning

confidence: 99%

The proto-oncogene Bcl3 induces immune checkpoint PD-L1 expression, mediating proliferation of ovarian cancer cells

Zou

Uddin

Padmanabhan

et al. 2018

Journal of Biological Chemistry

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The proto-oncogene Bcl3 induces survival and proliferation in cancer cells; however, its function and regulation in ovarian cancer (OC) remain unknown. Here, we show that expression is increased in human OC tissues. Surprisingly, however, we found that in addition to promoting survival, proliferation, and migration of OC cells, Bcl3 promotes both constitutive and interferon-γ (IFN)-induced expression of the immune checkpoint molecule PD-L1. The Bcl3 expression in OC cells is further increased by IFN, resulting in increased transcription. The mechanism consists of an IFN-induced, Bcl3- and p300-dependent promoter occupancy by Lys-314/315 acetylated p65 NF-κB. Blocking PD-L1 by neutralizing antibody reduces proliferation of OC cells overexpressing Bcl3, suggesting that the pro-proliferative effect of Bcl3 in OC cells is partly mediated by PD-L1. Together, this work identifies PD-L1 as a novel target of Bcl3, and links Bcl3 to IFNγ signaling and PD-L1-mediated immune escape.

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“…12,13 Bcl-3 promotes breast cancer metastasis 14 by stabilizing Smad3/TGFβ signaling. 15 In glioblastoma cells, Bcl-3 significantly facilitated proliferation by stabilizing the expression of STAT3, p-STAT3, and STAT3 signaling target genes, including Bcl-2, MCL-1, and cyclin D1. 16 Recently, the function of Bcl-3 in CRC has been reported by various research groups.…”

Section: Introductionmentioning

confidence: 98%

Bcl-3 promotes Wnt signaling by maintaining the acetylation of β-catenin at lysine 49 in colorectal cancer

Chen

Wang

Jiang

et al. 2020

Sig Transduct Target Ther

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Wnt/β-catenin signaling plays a critical role in colorectal cancer (CRC) tumorigenesis and the homeostasis of colorectal cancer stem cells (CSCs), but its molecular mechanism remains unclear. B-cell lymphoma 3 (Bcl-3), a member of the IκB family, is overexpressed in CRC and promotes tumorigenicity. Here, we report a novel function of Bcl-3 in maintaining colorectal CSC homeostasis by activating Wnt/β-catenin signaling. Silencing Bcl-3 suppresses the self-renewal capacity of colorectal CSCs and sensitizes CRC cells to chemotherapeutic drugs through a decrease in Wnt/β-catenin signaling. Moreover, our data show that Bcl-3 is a crucial component of Wnt/β-catenin signaling and is essential for β-catenin transcriptional activity in CRC cells. Interestingly, Wnt3a increases the level and nuclear translocation of Bcl-3, which binds directly to β-catenin and enhances the acetylation of β-catenin at lysine 49 (Ac-K49-β-catenin) and transcriptional activity. Bcl-3 depletion decreases the Ac-K49-β-catenin level by increasing the level of histone deacetylase 1 to remove acetyl groups from β-catenin, thus interrupting Wnt/β-catenin activity. In CRC clinical specimens, Bcl-3 expression negatively correlates with the overall survival of CRC patients. A significantly positive correlation was found between the expression of Bcl-3 and Ac-K49-β-catenin. Collectively, our data reveal that Bcl-3 plays a crucial role in CRC chemoresistance and colorectal CSC maintenance via its modulation of the Ac-K49-β-catenin, which serves as a promising therapeutic target for CRC.

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Bcl-3 regulates TGFβ signaling by stabilizing Smad3 during breast cancer pulmonary metastasis

Cited by 41 publications

References 46 publications

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

The proto-oncogene Bcl3 induces immune checkpoint PD-L1 expression, mediating proliferation of ovarian cancer cells

Bcl-3 promotes Wnt signaling by maintaining the acetylation of β-catenin at lysine 49 in colorectal cancer

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