Hsp90 chaperone facilitates E2F1/2-dependent gene transcription in human breast cancer cells

Kotwal, Akhil; Suran, Sourabh; Subbarao, Sreedhar Amere

doi:10.1016/j.ejcb.2020.151148

Cited by 8 publications

(9 citation statements)

References 44 publications

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“…E2F2 is a transcriptional activator. Although E2F2 has not been studied as carefully as E2F1, it plays a key role in many cellular processes such as cell cycle regulation, proliferation, differentiation, and cancer development [39][40][41]. Gao et al [42] have found that compared with the normal tissues, the miR-155 activity in ccRCC tissues is significantly upregulated.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma

Zhang

Cui

Wang

et al. 2021

Journal of Healthcare Engineering

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Background. E2F transcription factors is a family of transcription factors, and lots of studies have shown that they play a key role in the occurrence and development of many tumors. However, the association between expression, prognostic value, and immune infiltration in the tumor microenvironment of the eight E2Fs members in ccRCC is still unclear. Methods. We used online databases, such as ONCOMINE, UALCAN, Kaplan–Meier plotter, GEPIA, Metascape, TIMER, and cBioPortal, to analyze the effect of mRNA expression of E2Fs family members in ccRCC on the prognosis of patients and the relationship with immune infiltration. Results. Except for E2F5, other seven members of the family of E2Fs mRNA expression levels in ccRCC tissues were significantly higher than control tissues. And the high expression of E2Fs mRNA in ccRCC patients was related to cancer stage and tumor grade. Survival analysis results suggested that elevated mRNA expression levels of E2F1/2/3/4/7/8 were significantly related to the shorter overall survival (OS) in ccRCC patients ( P = 3.9E – 06), while high mRNA expression of E2F6 is not related to OS ( P = 0.061). Mutations of E2Fs were correlated with shorter OS of ccRCC patients ( P = 7.094E – 5). In addition, mRNA expression of E2F1/2/3/4/7/8 was positively correlated with infiltration of six types of immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions. These results indicate that E2F1/2/3/4/7/8 may be used as a prognostic marker for the survival of ccRCC patients and laid the foundation for studying the immune infiltration role of E2Fs family members in tumors.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma

Zhang

Cui

Wang

et al. 2021

Journal of Healthcare Engineering

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“…Amere Subbarao et al . ( 56 ) reported that HSP90 interacts with E2F1 and E2F2 in breast cancer cells with coimmunoprecipitation (co-IP) experiments earlier this year. Interestingly, they observed that E2F1 and E2F2 stability at the protein level was affected by the 17-AAG treatment in MCF-7 cells, whereas only E2F2 stability was affected in human embryonic kidney 293T cells.…”

Section: Discussionmentioning

confidence: 99%

“…Our data support that E2F1 positively regulates the transcription of 6 genes including CDC6, CDC45, MCM4, MCM7, PRIM1, and RMI2 in MCL cells. Amere Subbarao group reported that HSP90 interacts with E2F1 and E2F2 in breast cancer cells with co-IP experiments earlier this year (56). Interestingly, they observed E2F1 and E2F2 stability at the protein level was affected by the 17AAG treatment in MCF-7 cells, whereas only E2F2 stability was affected in HEK293T cells.…”

Section: Pre-treatment Of Ganetespib Sensitize MCL Cells To Mtor Inhibitorsmentioning

confidence: 98%

HSP90 inhibition downregulates DNA replication and repair genes via E2F1 repression

Liu

Shi

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…E2F1 has been attributed to numerous cancer hallmarks in prostate cancer, including cell cycle, proliferation and apoptosis [ 45 ], and its expression is so closely aligned with disease stage that it has been proposed as a potential biomarker [ 46 , 47 ]. Notably, AR, MYC and E2F1/2 are all established Hsp90 client proteins, and targeting Hsp90 inhibits expression of AR in prostate cancer (reviewed in [ 41 ]), and MYC [ 48 , 49 , 50 , 51 ] and E2F1 [ 52 , 53 ] in other cancers. Our ability to identify known pathways associated with Hsp90 and prostate cancer through omics analysis of PDE tissues highlights the capacity for omics identification of novel targets and biomarkers in the face of prostate tumor heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants

Centenera

Vincent

Moldovan

et al. 2022

Cancers

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Prostate cancer is a complex and heterogeneous disease, but a small number of cell lines have dominated basic prostate cancer research, representing a major obstacle in the field of drug and biomarker discovery. A growing lack of confidence in cell lines has seen a shift toward more sophisticated pre-clinical cancer models that incorporate patient-derived tumors as xenografts or explants, to more accurately reflect clinical disease. Not only do these models retain critical features of the original tumor, and account for the molecular diversity and cellular heterogeneity of prostate cancer, but they provide a unique opportunity to conduct research in matched tumor samples. The challenge that accompanies these complex tissue models is increased complexity of analysis. With over 10 years of experience working with patient-derived explants (PDEs) of prostate cancer, this study provides guidance on the PDE method, its limitations, and considerations for addressing the heterogeneity of prostate cancer PDEs that are based on statistical modeling. Using inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) as an example of a drug that induces robust proliferative response, we demonstrate how multi-omics analysis in prostate cancer PDEs is both feasible and essential for identification of key biological pathways, with significant potential for novel drug target and biomarker discovery.

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Hsp90 chaperone facilitates E2F1/2-dependent gene transcription in human breast cancer cells

Cited by 8 publications

References 44 publications

Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma

Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma

HSP90 inhibition downregulates DNA replication and repair genes via E2F1 repression

Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants

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