TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression

Fong, Ka Wing; Zhao, Jonathan C.; Song, Bing; Zheng, Bin; Yu, Jindan

doi:10.1038/s41467-018-07475-5

Cited by 91 publications

(89 citation statements)

References 56 publications

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“…The treatment of PCa has attracted increasing attention in recent years (12). Previous studies have reported numerous gene targets that were able to inhibit cell proliferation and promote apoptosis in PCa (21)(22)(23). A recent study has suggested that certain natural products, such as green tea, can effectively induce apoptosis and inhibit invasion of PCa cells via the PI3K/Akt signaling pathway (24).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of GSG2 inhibits prostate cancer progression in�vitro and in�vivo

Lin

et al. 2020

Int J Oncol

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Prostate cancer (PCa) is the second leading cause of cancer-related death among men worldwide. The present study aimed to investigate the role of germ cell-specific gene 2 protein (GSG2), also termed histone H3 phosphorylated by GSG2 at threonine-3, in the development and progression of PCa. GSG2 expression levels in PCa tissues and para-carcinoma tissues was detected by immunohistochemistry. The GSG2 knockdown cell model was constructed by lentivirus infection, and the knockdown efficiency was verified by qPCR and WB. In addition, the effects of shGSG2 on cell proliferation, colony formation and apoptosis were evaluated by Celigo cell counting assay, Giemsa staining and flow cytometry, respectively. Tumor development in nude mice was also detected. GSG2 expression was upregulated in PCa tissues and human PCa cell lines PC-3 and DU 145. High expression of GSG2 in tumor samples was associated with progressed tumors. GSG2 knockdown suppressed cell proliferation and colony formation, but promoted apoptosis, which was also verified in vivo.The results of the present study revealed that GSG2 upregulation was associated with PCa progression; GSG2 knockdown inhibited cell proliferation and colony formation and induced apoptosis, and may therefore serve as a potential therapeutic target for PCa therapy.

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Section: Discussionmentioning

confidence: 99%

Knockdown of GSG2 inhibits prostate cancer progression in�vitro and in�vivo

Lin

et al. 2020

Int J Oncol

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“…Several of the EN1-interacting proteins common between the two cell lines represent transcriptional cofactors TLE3 and TRIM28 (25), and nuclear hormone receptor coactivators TRIM33 and TRIM24. Interestingly TRIM28 was recently identified as a critical regulator of TRIM24, an oncogene in prostate cancer (26) and TRIM24-TRIM28-TRIM33 complex has previously been identified as a suppressor of murine hepatocellular carcinoma growth (27). Because of prior data implying a functional role for the TLE3-EN1 interaction during development (23), we further explored the relevance of this association in breast cancer cells.…”

Section: En1 Interacting Proteins In Breast Cancer Cellsmentioning

confidence: 99%

EN1 Is a Transcriptional Dependency in Triple-Negative Breast Cancer Associated with Brain Metastasis

et al. 2019

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To define transcriptional dependencies of triple-negative breast cancer (TNBC), we identified transcription factors highly and specifically expressed in primary TNBCs and tested their requirement for cell growth in a panel of breast cancer cell lines. We found that EN1 (engrailed 1) is overexpressed in TNBCs and its downregulation preferentially and significantly reduced viability and tumorigenicity in TNBC cell lines. By integrating gene expression changes after EN1 downregulation with EN1 chromatin binding patterns, we identified genes involved in WNT and Hedgehog signaling, neurogenesis, and axonal guidance as direct EN1 transcriptional targets. Quan-titative proteomic analyses of EN1-bound chromatin complexes revealed association with transcriptional repressors and coactivators including TLE3, TRIM24, TRIM28, and TRIM33. High expression of EN1 correlated with short overall survival and increased risk of developing brain metastases in patients with TNBC. Thus, EN1 is a prognostic marker and a potential therapeutic target in TNBC.Significance: These findings show that the EN1 transcription factor regulates neurogenesis-related genes and is associated with brain metastasis in triple-negative breast cancer.

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“…To test this, we performed subcutaneous injections of A375 cells stably transduced with shT28-1 or shSCR lentivirus. Indeed, in contrast to its role in breast and prostate cancer cells 8,9 , knockdown of TRIM28 in melanoma cells led to more rapid tumor growth (Fig. 2e, f).…”

Section: Figurementioning

confidence: 89%

“…2c, d). TRIM28 has previously been reported to promote growth of breast and prostate cancer 8,9 . However, the increased levels of the mitogenic and angiogenic factors CXCL1, CXCL2 and CXCL8 17 after TRIM28 knockdown suggested that TRIM28 instead suppresses the growth of melanoma tumors.…”

Section: Figurementioning

confidence: 99%

Melanoma plasticity is controlled by a TRIM28-JUNB mediated switch

Nyberg

Sjöstrand

et al. 2019

Preprint

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The introduction of immune checkpoint blockade has revolutionized the treatment of metastatic melanoma1. However, 40-60% of patients with metastatic melanoma do not respond to immune checkpoint blockade, and a significant fraction of patients acquire resistance to treatment2,3. This resilience and aggressiveness of melanoma tumors is partly due to their ability to switch between invasive and proliferative states4,5. The transition between phenotypic states indicates that phenotype switching occurs through reversible epigenetic mechanisms rather than by acquisition of mutations6,7. Identifying the epigenetic mechanisms that underlie phenotype switching of melanoma cells could potentially lead to new therapeutic strategies. Here we report that the bromodomain protein TRIM28 (KAP1/TIF1β) regulates a JUNB dependent phenotypic switch in melanoma cells. Knockdown of TRIM28 in melanoma cells reduced the expression of pro-invasive YAP1 signature genes, and led to reduced invasiveness and lung colonization. In contrast, TRIM28 knockdown increased the expression of KRAS signature genes and promoted tumor growth. TRIM28 interacted with the transcriptional elongation factors CDK9 and HEXIM1, and negatively regulated the transcriptional elongation of JUNB by RNA polymerase II. Rescue experiments demonstrated that the effects of TRIM28 knockdown were directly mediated by JUNB. Mechanistically, JUNB played a pivotal role in phenotype switching by inhibiting the invasiveness of melanoma cells and increasing the growth of melanoma tumors. Our results contribute to the understanding of melanoma plasticity, and suggest that cancer drugs inhibiting the transcriptional elongation of RNA polymerase II should be carefully evaluated in melanoma to exclude the risk for increased metastasis.

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TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression

Cited by 91 publications

References 56 publications

Knockdown of GSG2 inhibits prostate cancer progression in�vitro and in�vivo

Knockdown of GSG2 inhibits prostate cancer progression in�vitro and in�vivo

EN1 Is a Transcriptional Dependency in Triple-Negative Breast Cancer Associated with Brain Metastasis

Melanoma plasticity is controlled by a TRIM28-JUNB mediated switch

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