Histone chaperone FACT complex coordinates with HIF to mediate an expeditious transcription program to adapt to poorly oxygenated cancers

Shen, Jialing; Yang, Chunxue; Zhang, Misty Shuo; Chin, Don Wai‐Ching; Chan, For-Fan; Law, Cheuk‐Ting; Wang, Gengchao; Cheng, Carol Lai‐Hung; Chen, Mengnuo; Wan, Rebecca Ting-Chi; Wu, Mengjie; Kuang, Zhijian; Sharma, Rakesh; Lee, Terence; Ng, Irene Oi Lin; Wong, Carmen Chak‐Lui; Wong, Chun Ming

doi:10.1016/j.celrep.2022.110304

Cited by 9 publications

(6 citation statements)

References 41 publications

(55 reference statements)

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“…( A ) Potential implication of FACT complex in NRF2/KEAP1 pathway. FACT complex works in tandem with NRF2, establishing a positive feedback loop to over-express antioxidant proteins [ 31 ]. ( B ) A potential implication of the FACT complex in the ATR/CHK1 pathway is to prevent replication stress in response to DNA damage [ 22 , 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…Defining the FACT complex as a novel target for cancer treatment enabled researchers to investigate Curaxin as a therapeutic treatment for HCC patients [ 32 ]. Curaxin, a small molecular inhibitor of FACT that induces chromatin trapping of FACT and significantly inhibits normal human FACT activities, causes intracellular acidification and apoptosis of cancer cells [ 31 , 33 ]. Curaxin treatment has been shown to block the gene expressions needed for oxidative stress and hypoxia responses in HCC cells, presumably in correlation with the FACT complex’s interaction with NRF2 [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

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Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

Lee,

Bao

2024

IJMS

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Histone chaperones are integral to chromatin dynamics, facilitating the assembly and disassembly of nucleosomes, thereby playing a crucial role in regulating gene expression and maintaining genomic stability. Moreover, they prevent aberrant histone interactions prior to chromatin assembly. Disruption in histone chaperone function may result in genomic instability, which is implicated in pathogenesis. This review aims to elucidate the role of histone chaperones in cancer pathologies and explore their potential as therapeutic targets. Histone chaperones have been found to be dysregulated in various cancers, with alterations in expression levels, mutations, or aberrant interactions leading to tumorigenesis and cancer progression. In addition, this review intends to highlight the molecular mechanisms of interactions between histone chaperones and oncogenic factors, underscoring their roles in cancer cell survival and proliferation. The dysregulation of histone chaperones is significantly correlated with cancer development, establishing them as active contributors to cancer pathology and viable targets for therapeutic intervention. This review advocates for continued research into histone chaperone-targeted therapies, which hold potential for precision medicine in oncology. Future advancements in understanding chaperone functions and interactions are anticipated to lead to novel cancer treatments, enhancing patient care and outcomes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

Lee,

Bao

2024

IJMS

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“…Under hypoxic conditions, HIF‐1α and HIF‐2α exhibit robust expression in HCC; these expression patterns contribute to increased production of angiogenic factors, such as vascular endothelial growth factor (VEGF), to drive angiogenesis 101 . Hypoxia‐inducible factor 1 (HIF‐1), a transcription factor that rapidly activates a range of gene transcription, can ensure the survival of cancer cells in hypoxia and further imbue cancer cells with aggressive properties (self‐renewal, metastasis, angiogenesis and treatment resistance) 102 . Sorafenib‐focused studies have shown that hypoxic can induce sorafenib resistance, and HIF‐1a or HIF‐2α inhibitors with different mechanisms can improve outcomes 101,103–105 .…”

Section: Possible Mechanisms Of Resistance To Lenvatinibmentioning

confidence: 99%

“…101 Hypoxia-inducible factor 1 (HIF-1), a transcription factor that rapidly activates a range of gene transcription, can ensure the survival of cancer cells in hypoxia and further imbue cancer cells with aggressive properties (self-renewal, metastasis, angiogenesis and treatment resistance). 102 Sorafenib-focused studies have shown that hypoxic can induce sorafenib resistance, and HIF-1a or HIF-2α inhibitors with different mechanisms can improve outcomes. 101,[103][104][105] Hypoxia is also strongly associated with the lenvatinib response in HCC.…”

Section: Hypoxiamentioning

confidence: 99%

Lenvatinib in hepatocellular carcinoma: Resistance mechanisms and strategies for improved efficacy

Qin,

Han,

et al. 2024

Liver International

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Hepatocellular carcinoma (HCC), one of the most prevalent and destructive causes of cancer‐related deaths worldwide, approximately 70% of patients with HCC exhibit advanced disease at diagnosis, limiting the potential for radical treatment. For such patients, lenvatinib, a long‐awaited alternative to sorafenib for first‐line targeted therapy, has become a key treatment. Unfortunately, despite some progress, the prognosis for advanced HCC remains poor because of drug resistance development. However, the molecular mechanisms underlying lenvatinib resistance and ways to relief drug resistance in HCC are largely unknown and lack of systematic summary; thus, this review not only aims to explore factors contributing to lenvatinib resistance in HCC, but more importantly, summary potential methods to conquer or mitigate the resistance. The results suggest that abnormal activation of pathways, drug transport, epigenetics, tumour microenvironment, cancer stem cells, regulated cell death, epithelial–mesenchymal transition, and other mechanisms are involved in the development of lenvatinib resistance in HCC and subsequent HCC progression. To improve the therapeutic outcomes of lenvatinib, inhibiting acquired resistance, combined therapies, and nano‐delivery carriers may be possible approaches.

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“…This suggests that it may be interesting to try CBL0137 in combination with ICB, which can be enhanced by innate immune activation, including IFNg [ 296 ]. Finally, FACT has been demonstrated to mediate adaptation to hypoxia and CBL0137 impaired tumor growth and enhances the effects of an anti-angiogenic drug, bevacizumab, in a hepatocellular carcinoma model [ 297 ]. While the effects of CBL0137 have not been reported in PCa, it has entered clinical trials for a number of other cancer types, and its potential to enhance genotoxic agents, impair transcription, sensitize hypoxic cells, and improve DDR inhibitor and ICB responses may be useful to explore in future work (NCT01905228, NCT02931110, NCT03727789, NCT05498792, NCT04870944).…”

Section: Emerging Targets In Crpcmentioning

confidence: 99%

Exploiting the DNA Damage Response for Prostate Cancer Therapy

Stracker,

Osagie,

Escorcia

et al. 2023

Cancers

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Prostate cancers that progress despite androgen deprivation develop into castration-resistant prostate cancer, a fatal disease with few treatment options. In this review, we discuss the current understanding of prostate cancer subtypes and alterations in the DNA damage response (DDR) that can predispose to the development of prostate cancer and affect its progression. We identify barriers to conventional treatments, such as radiotherapy, and discuss the development of new therapies, many of which target the DDR or take advantage of recurring genetic alterations in the DDR. We place this in the context of advances in understanding the genetic variation and immune landscape of CRPC that could help guide their use in future treatment strategies. Finally, we discuss several new and emerging agents that may advance the treatment of lethal disease, highlighting selected clinical trials.

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Histone chaperone FACT complex coordinates with HIF to mediate an expeditious transcription program to adapt to poorly oxygenated cancers

Cited by 9 publications

References 41 publications

Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

Lenvatinib in hepatocellular carcinoma: Resistance mechanisms and strategies for improved efficacy

Exploiting the DNA Damage Response for Prostate Cancer Therapy

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