Supplementary Table S1 from Androgen Receptor Signaling Regulates DNA Repair in Prostate Cancers

Polkinghorn, William R.; Parker, Joel S.; Lee, Man X.; Kass, Elizabeth M.; Spratt, Daniel E.; Iaquinta, Phillip J.; Arora, Vivek K.; Yen, Wei-Feng; Cai, Ling; Zheng, Deyou; Carver, Brett S.; Chen, Yu; Watson, Philip A.; Shah, Neel; Fujisawa, Sho; Goglia, Alexander G.; Gopalan, Anuradha; Hieronymus, Haley; Wongvipat, John; Scardino, Peter T.; Zeléfsky, Michael J.; Jasin, Maria; Chaudhuri, Jayanta; Powell, Simon N.; Sawyers, Charles L.

doi:10.1158/2159-8290.22529279

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“…Although the mechanism for this resistance couldn't be elucidated from our data, it is likely to involve apoptosis resistance mechanisms given the role of HSP90 alpha in regulating DNAPK activation and apoptosis [31]. Since AR is known to be involved with the transcription of genes of DNA damage and response pathway [11,12], we hypothesized that downregulation of AR function upon AR inhibition might affect the expression of DNA damage response pathway genes, making it vulnerable to DNA repair pathway inhibitors.…”

Section: Discussionmentioning

confidence: 94%

“…6H). Micronuclei result from chromosomal instability and have been linked to faulty homologous recombination DNA repair (11). To investigate whether inhibition of CRM1 affects HR repair, we performed a fluorescent protein-based homologous recombination assay (12).…”

Section: Crm1 Affects Dna Repair Function In Prostate Cancer Cellsmentioning

confidence: 99%

“…Although CRM1 is known to regulate the nuclear export of various DNA repair enzymes and proteins, the exact role of CRM1 in major DNA repair pathways remains understudied. In prostate cancer, the androgen receptor plays an important role in the transcriptional regulation of DNA repair genes [11,12]. However, whether inhibition of CRM1 transcriptionally impacts DNA repair via the androgen receptor is unknown.…”

Section: Introductionmentioning

confidence: 99%

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CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor

Kumar,

Mendonca,

Shetty

et al. 2024

Preprint

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Among the known nuclear exportins, CRM1 is the most studied prototype. Dysregulation of CRM1 occurs in many cancers, hence, understanding the role of CRM1 in cancer can help in developing synergistic therapeutics. The study investigates how CRM1 affects prostate cancer growth and survival. It examines the role of CRM1 in regulating androgen receptor (AR) and DNA repair in prostate cancer. Our findings reveal that CRM1 influences AR mRNA and protein stability, leading to a loss of AR protein upon CRM1 inhibition. Furthermore, it highlights the involvement of HSP90 alpha, a known AR chaperone, in the CRM1-dependent regulation of AR protein stability. The combination of CRM1 inhibition with an HSP90 inhibitor demonstrates potent effects on decreasing prostate cancer cell growth and survival. The study further explores the influence of CRM1 on DNA repair proteins and proposes a strategy of combining CRM1 inhibitors with DNA repair pathway inhibitors to decrease prostate cancer growth. Overall, the findings suggest that CRM1 plays a crucial role in prostate cancer growth, and a combination of inhibitors targeting CRM1 and DNA repair pathways could be a promising therapeutic strategy.

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Section: Discussionmentioning

confidence: 94%

Section: Crm1 Affects Dna Repair Function In Prostate Cancer Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor

Kumar,

Mendonca,

Shetty

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Supplementary Table S1 from Androgen Receptor Signaling Regulates DNA Repair in Prostate Cancers

Abstract: <p>Supplementary Table S1 - PDF file 170K, Gene set enrichment analysis of ARN-509-treated LNCaP-AR xenografts</p>

Cited by 1 publication

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CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor

CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor

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