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Mithramycin and its analogs: Molecular features and antitumor action.
Pharmacol Ther
August 2024
Instituto de Diagnóstico Ambiental y Estudios del Agua, CSIC, E-08034 Barcelona, Spain. Electronic address:
The antitumor antibiotic mithramycin A (MTA) binds to G/C-rich DNA sequences in the presence of dications. MTA inhibits transcription regulated by the Sp1 transcription factor, often enhanced during tumor development. It shows antitumor activity, but its clinical use was discontinued due to toxic side effects.
View Article and Find Full Text PDFIdentification of an anaplastic subtype of prostate cancer amenable to therapies targeting SP1 or translation elongation.
Sci Adv
April 2024
The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha 410082, Hunan Province, China.
Article Synopsis
- Prostate cancer exhibits significant histopathological diversity, and a new subtype identified as small cell-like PCa (SCLPC) shows aggressive clinical behavior with low androgen receptor activity but high stemness and proliferation.
- This subtype is characterized by a molecular profile associated with protein translation, including overexpression of ribosomal protein genes and SP1, a transcription factor linked to castration-resistant PCa (CRPC).
- Targeted therapies like the SP1 inhibitor plicamycin and the translation elongation inhibitor homoharringtonine demonstrate potential in reducing CRPC growth and progression, highlighting these pathways as promising avenues for clinical treatment.
Three-dimensional chromatin analysis reveals Sp1 as a mediator to program and reprogram HPV-host epigenetic architecture in cervical cancer.
Cancer Lett
April 2024
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:
Article Synopsis
- HPV is linked to various cancers, but the exact mechanisms behind its interaction with host cells' genetics are not fully understood.
- Researchers used advanced mapping techniques to study how HPV interacts with the host's chromatin and identified the transcription factor Sp1 as a crucial player in these interactions.
- Targeting Sp1 can not only reduce oncogene activity related to HPV but also enhance immune responses, suggesting that Sp1 inhibition could be a potential treatment strategy for HPV-related cancers, especially in cervical cancer patients.
The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells.
Exp Cell Res
December 2023
Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, 44121 Ferrara, Italy; Center 'Chiara Gemmo and Elio Zago' for the Research on Thalassemia, University of Ferrara, 44121 Ferrara, Italy. Electronic address:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causative of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV-2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, that were fundamental for the reduction of the viral spread within the population and the clinical severity of COVID-19.
View Article and Find Full Text PDFELK4 Promotes Colorectal Cancer Progression by Activating the Neoangiogenic Factor LRG1 in a Noncanonical SP1/3-Dependent Manner.
Adv Sci (Weinh)
November 2023
Department of Colorectal and Anal Surgery, Shanghai Colorectal Cancer Research Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Article Synopsis
- The MAPK/MEK/ERK pathway is commonly activated in colorectal cancer (CRC), but MEK/ERK inhibitors have limited clinical effectiveness.
- Research indicates that ELK4 plays a crucial role in promoting CRC tumor growth by forming a complex with transcription factors SP1 and SP3, rather than the previously thought SRF.
- Targeting the ELK4-SP1/SP3 complex using MEK/ERK inhibitors combined with the SP1 inhibitor mithramycin A shows promising anti-tumor effects, and ELK4 serves as a potential prognostic marker for CRC.
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