SUMOylation Controls the Binding of Hexokinase 2 to Mitochondria and Protects against Prostate Cancer Tumorigenesis

Investigators report that SUMOylation regulated the binding of hexokinase 2 to mitochondria. They found that hexokinase 2 could be SUMOylated at K315 and K492.
[Nature Communications]
Shangguan, X., He, J., Ma, Z., Zhang, W., Ji, Y., Shen, K., Yue, Z., Li, W., Xin, Z., Zheng, Q., Cao, Y., Pan, J., Dong, B., Cheng, J., Wang, Q., & Xue, W. (2021). SUMOylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis. Nature Communications, 12(1), 1812. https://doi.org/10.1038/s41467-021-22163-7 Cite
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Pin1 Inhibition Improves the Efficacy of Ralaniten Compounds That Bind to the N-Terminal Domain of Androgen Receptor

The authors showed that Pin1 interacted with androgen receptor (AR) N-terminal domain. The inhibition of Pin1 expression or its activity selectively reduced the transcriptional activities of full-length AR and AR-V7.
[Communications Biology]
Leung, J. K., Imamura, Y., Kato, M., Wang, J., Mawji, N. R., & Sadar, M. D. (2021). Pin1 inhibition improves the efficacy of ralaniten compounds that bind to the N-terminal domain of androgen receptor. Communications Biology, 4(1), 1–16. https://doi.org/10.1038/s42003-021-01927-3 Cite
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EZH2 Inhibition Activates a dsRNA–STING–Interferon Stress Axis That Potentiates Response to PD-1 Checkpoint Blockade in Prostate Cancer

Scientists demonstrated that enhancer of zeste homolog-2 (EZH2) inhibition in prostate cancer models activated a double-stranded RNA–STING–ISG stress response upregulating genes involved in antigen presentation, Th1 chemokine signaling and interferon response, including programmed cell death protein 1 (PD-L1) that was dependent on STING activation.
[Nature Cancer]
Morel, K. L., Sheahan, A. V., Burkhart, D. L., Baca, S. C., Boufaied, N., Liu, Y., Qiu, X., Cañadas, I., Roehle, K., Heckler, M., Calagua, C., Ye, H., Pantelidou, C., Galbo, P., Panja, S., Mitrofanova, A., Wilkinson, S., Whitlock, N. C., Trostel, S. Y., … Ellis, L. (2021). EZH2 inhibition activates a dsRNA–STING–interferon stress axis that potentiates response to PD-1 checkpoint blockade in prostate cancer. Nature Cancer, 1–13. https://doi.org/10.1038/s43018-021-00185-w Cite
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Progression of Prostate Carcinoma Is Promoted by Adipose Stromal Cell-Secreted CXCL12 Signaling in Prostate Epithelium

Researchers demonstrated that epithelial–mesenchymal transition in prostate tumors was promoted by obesity and suppressed upon pharmacological adipose stromal cells depletion in HiMyc mice, a spontaneous genetic model of prostate cancer.
[npj Precision Oncology]
Su, F., Daquinag, A. C., Ahn, S., Saha, A., Dai, Y., Zhao, Z., DiGiovanni, J., & Kolonin, M. G. (2021). Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium. Npj Precision Oncology, 5(1), 1–10. https://doi.org/10.1038/s41698-021-00160-9 Cite
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Using CT-Guided Stereotactic Prostate Radiation Therapy (CT-SPRT) to Assess Sustained Murine Prostate Ablation

Investigators designed a novel computed-tomography (CT)–SPRT technique to deliver a single high-dose 25 Gy fraction of X-ray radiation.
[Scientific Reports]
Zahalka, A. H., Brodin, N. P., Maryanovich, M., Wang, X., Watts, K. L., Pinho, S., Guha, C., & Frenette, P. S. (2021). Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation. Scientific Reports, 11(1), 6571. https://doi.org/10.1038/s41598-021-86067-8 Cite
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Resistance to Second-Generation Androgen Receptor Antagonists in Prostate Cancer

Ongoing research to establish predictive biomarkers for the treatment of tumors with resistance to second-generation androgen receptor antagonists led to the approval of the PARP inhibitors olaparib and rucaparib in pre-treated metastatic castration-resistant prostate cancer.
[Nature Reviews Urology]
Schmidt, K. T., Huitema, A. D. R., Chau, C. H., & Figg, W. D. (2021). Resistance to second-generation androgen receptor antagonists in prostate cancer. Nature Reviews Urology, 1–18. https://doi.org/10.1038/s41585-021-00438-4 Cite
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CRISPRi Screens Reveal a DNA Methylation-Mediated 3D Genome Dependent Causal Mechanism in Prostate Cancer

Scientists performed CRISPRi screens of 260 cis-regulatory elements (rCREs) in prostate cancer cell lines. They found that rCREs harboring high risk SNPs were more essential for cell proliferation and H3K27ac occupancy was a strong indicator of essentiality.
[Nature Communications]
Ahmed, M., Soares, F., Xia, J.-H., Yang, Y., Li, J., Guo, H., Su, P., Tian, Y., Lee, H. J., Wang, M., Akhtar, N., Houlahan, K. E., Bosch, A., Zhou, S., Mazrooei, P., Hua, J. T., Chen, S., Petricca, J., Zeng, Y., … He, H. H. (2021). CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer. Nature Communications, 12(1), 1781. https://doi.org/10.1038/s41467-021-21867-0 Cite
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Oxytocin Receptor Antagonists as a Novel Pharmacological Agent for Reducing Smooth Muscle Tone in the Human Prostate

The authors investigated the effects of exogenous oxytocin on both stromal cell proliferation, and inherent spontaneous prostate contractions using primary models derived from human prostate tissue.
[Scientific Reports]
Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate | Scientific Reports. (n.d.). Retrieved March 18, 2021, from https://www.nature.com/articles/s41598-021-85439-4 Cite
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Acetylation of KLF5 Maintains EMT and Tumorigenicity to Cause Chemoresistant Bone Metastasis in Prostate Cancer

Investigators report that bone-borne TGF-β induced the acetylation of transcription factor KLF5 in prostate cancer bone metastases, and acetylated KLF5 caused osteoclastogenesis and bone metastatic lesions by activating CXCR4, which led to IL-11 secretion, and stimulated SHH/IL-6 paracrine signaling.
[Nature Communications]
Zhang, B., Li, Y., Wu, Q., Xie, L., Barwick, B., Fu, C., Li, X., Wu, D., Xia, S., Chen, J., Qian, W. P., Yang, L., Osunkoya, A. O., Boise, L., Vertino, P. M., Zhao, Y., Li, M., Chen, H.-R., Kowalski, J., … Dong, J.-T. (2021). Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer. Nature Communications, 12(1), 1714. https://doi.org/10.1038/s41467-021-21976-w Cite
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Vinculin Orchestrates Prostate Cancer Progression by Regulating Tumor Cell Invasion, Migration, and Proliferation

Researchers investigated the potential role of vinculin in prostate cancer progression in vitro and in vivo.
[Prostate]
Zheng, X., Xu, H., Gong, L., Cao, D., Jin, T., Wang, Y., Pi, J., Yang, Y., Yi, X., Liao, D., Jin, X., Wei, Q., Yang, L., Li, H., & Ai, J. (n.d.). Vinculin orchestrates prostate cancer progression by regulating tumor cell invasion, migration, and proliferation. The Prostate, n/a(n/a). https://doi.org/https://doi.org/10.1002/pros.24113 Cite
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Host Versus Cell-Dependent Effects of β-Arrestin-1 Expression in Prostate Tumorigenesis

The authors investigated the effect of β-arrestin 1 overexpression in prostate cancer development and progression using the mouse and human prostate cancer cell xenografts, and autochthonous transgenic adenocarcinoma mouse prostate models deficient in β-arrestins.
[Carcinogenesis]
Adekoya, T. O., Smith, N., Thomas, A. J., Lane, T. S., Burnette, N., Rivers, E. J., Li, Y., Chen, X. L., & Richardson, R. M. (2021). Host versus cell-dependent effects of β-Arrestin-1 expression in prostate tumorigenesis. Carcinogenesis, bgab021. https://doi.org/10.1093/carcin/bgab021 Cite
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