Cisplatin‐induced <scp>HSF1‐HSP90</scp> axis enhances the expression of functional <scp>PD‐L1</scp> in oral squamous cell carcinoma

Sasaya, Takashi; Kubo, Terufumi; Murata, Kenji; Mizue, Yuka; Sasaki, Kenta; Yanagawa, Junko; Imagawa, Makoto; Kato, Hirotaka; Tsukahara, Tomohide; Kanaseki, Takayuki; Tamura, Yasuaki; Miyazaki, Akira; Hirohashi, Yoshihiko; Torigoe, Toshihiko

doi:10.1002/cam4.5310

Cited by 14 publications

(17 citation statements)

References 51 publications

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“…Our data also suggested that tumors' stress levels differed among clinical cases (Figures 4,5). Tumor cells are characteristically exposed to various stresses from the microenvironment, such as immune/inflammatory stress [19], therapeutics [18], hypoxia [22,[52][53][54][55], acidification [56,57], hyperthermia [58,59] or heat stress [4,6,19,25,28], endoplasmic reticulum stress [60], nuclear envelope stress [61,62], replication stress [63], oxidative stress [64], mechanical stress, osmotic stress, genotoxic (DNA damage) [65,66] and proteotoxic stress [1,2,4,67]. Therefore, it might be difficult to determine the types and levels of stresses in each tumor.…”

Section: Discussionmentioning

confidence: 54%

“…MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content. observed in many cancer types and correlates with poor prognosis, increased metastatic potential and resistance to therapy [16][17][18][19]. Moreover, the HSP90 alpha and beta isoforms are often released with extracellular vesicles (EV), including exosomes, by cancer cells and can thus trigger cancer initiation and progression, as well as the polarization of tumorassociated macrophages to an immunosuppressive M2 subtype [6,17,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Stress-inducible SCAN Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers

Eguchi¹,

Sheta²,

Calderwood³

2023

Preprint

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The cell stress response is an essential system present in every cell for responding and adapting to extracellular environmental stimulations. A major program for stress response is the heat shock factor (HSF)–heat shock protein (HSP) system that maintains proteostasis in cells and promotes cancer progression. However, less is known about how the cell stress response is regulated by alternative transcription factors. Here, we show that the SCAN domain-containing transcription factors (SCAN-TFs) are involved in repressing the stress response in cancer. SCAND1 and SCAND2 are SCAN-TFs that can hetero-oligomerize with SCAN-zinc finger transcription factors, such as MZF1(ZSCAN6), for accessing DNA and transcriptionally co-repressing target genes. We found that heat stress induced the expression of both SCAND1 and MZF1(ZSCAN6) bound to HSP90 gene promoter regions in prostate cancer cells. SCAND1 and MZF1 blocked the heat shock responsiveness of HSP90 in prostate cancer cells. Gene expression of SCAND2, SCAND1 and MZF1 was negatively correlated with HSP90 expression in patients-derived prostate adenocarcinoma. MZF1 and SCAND2 were more highly expressed in paired normal tissues than in tumor tissues in several cancer types. High expression of SCAND2, SCAND1 and MZF1 correlated with enhanced prognoses of pancreatic cancer and head and neck cancers. Additionally, high expression of SCAND2 was correlated with better prognoses of lung adenocarcinoma and sarcoma. In contrast, high expression of HSP90AA1 correlated with poorer prognoses in several cancer types. These data suggest that the stress-inducible SCAN-TFs can function as a feedback system, suppressing excessive stress response and inhibiting cancers.

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Stress-inducible SCAN Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers

Eguchi¹,

Sheta²,

Calderwood³

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Our data also suggested that tumors’ stress levels differs among clinical cases ( Figure 7 ). Tumor cells are characteristically exposed to various stresses from the microenvironment, such as immune/inflammatory stress [ 19 ], therapeutics [ 18 ], hypoxia [ 22 , 58 , 59 , 60 , 61 ], acidification [ 62 , 63 ], hyperthermia [ 64 , 65 ] or heat stress [ 4 , 6 , 19 , 25 , 28 ], endoplasmic reticulum stress [ 66 ], nuclear envelope stress [ 67 , 68 ], replication stress [ 69 ], oxidative stress [ 70 ], mechanical stress, osmotic stress, and genotoxic (DNA damage) [ 71 , 72 ] and proteotoxic stress [ 1 , 2 , 4 , 73 ]. Therefore, it might be difficult to determine the types and levels of stresses in each tumor.…”

Section: Discussionmentioning

confidence: 99%

“…As HSP90 has several hundred protein substrates (called ‘clients’), it is involved in many cellular processes beyond protein folding, which include DNA repair, development, the immune response, and neurodegeneration [ 11 , 12 , 13 , 14 , 15 ]. Elevated expression of HSP90 has been observed in many cancer types and correlates with poor prognosis, increased metastatic potential, and resistance to therapy [ 16 , 17 , 18 , 19 ]. Moreover, the HSP90 alpha and beta isoforms are often released with extracellular vesicles (EV), including exosomes, by cancer cells and trigger cancer initiation and progression, as well as the polarization of tumor-associated macrophages (TAM) to an immunosuppressive M2 subtype [ 6 , 17 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Stress-Inducible SCAND Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers

Sheta

Yoshida

Kanemoto

et al. 2023

IJMS

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The cell stress response is an essential system present in every cell for responding and adapting to environmental stimulations. A major program for stress response is the heat shock factor (HSF)–heat shock protein (HSP) system that maintains proteostasis in cells and promotes cancer progression. However, less is known about how the cell stress response is regulated by alternative transcription factors. Here, we show that the SCAN domain (SCAND)-containing transcription factors (SCAN-TFs) are involved in repressing the stress response in cancer. SCAND1 and SCAND2 are SCAND-only proteins that can hetero-oligomerize with SCAN-zinc finger transcription factors, such as MZF1(ZSCAN6), for accessing DNA and transcriptionally co-repressing target genes. We found that heat stress induced the expression of SCAND1, SCAND2, and MZF1 bound to HSP90 gene promoter regions in prostate cancer cells. Moreover, heat stress switched the transcript variants’ expression from long noncoding RNA (lncRNA-SCAND2P) to protein-coding mRNA of SCAND2, potentially by regulating alternative splicing. High expression of HSP90AA1 correlated with poorer prognoses in several cancer types, although SCAND1 and MZF1 blocked the heat shock responsiveness of HSP90AA1 in prostate cancer cells. Consistent with this, gene expression of SCAND2, SCAND1, and MZF1 was negatively correlated with HSP90 gene expression in prostate adenocarcinoma. By searching databases of patient-derived tumor samples, we found that MZF1 and SCAND2 RNA were more highly expressed in normal tissues than in tumor tissues in several cancer types. Of note, high RNA expression of SCAND2, SCAND1, and MZF1 correlated with enhanced prognoses of pancreatic cancer and head and neck cancers. Additionally, high expression of SCAND2 RNA was correlated with better prognoses of lung adenocarcinoma and sarcoma. These data suggest that the stress-inducible SCAN-TFs can function as a feedback system, suppressing excessive stress response and inhibiting cancers.

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“…Additionally, studies are underway to test whether inhibition of HSF1 with small molecular inhibitors, such as DTHIB (74), can result in the same influx of CD8+ T cells, which could prime the targeting of HSF1 as a potential clinical approach to making breast cancer cells more immune cell-rich. Lastly, the role of HSF1 in CD8+ T cell activity or exhaustion warrants further investigation considering HSF1 has been reported to upregulate PD-L1 expression on cancer cells (75,76). These results generate several new lines of investigation for the role of HSF1 in new aspects of tumor biology and tumor-immune interactions.…”

Section: Discussionmentioning

confidence: 99%

HSF1 excludes CD8+ T cells from breast tumors via suppression of CCL5

Carpenter

Ray

Wang

et al. 2022

Preprint

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Cells have evolved mechanisms for response to external stressors in order to maintain cell viability in the face of changes in the environment. The response to heat stress is driven by the transcription factor heat shock factor 1 (HSF1), which is considered the master regulator of the heat shock response. Here we report a new HSF1 gene signatured termed “HSF1 Activity Signature,” or HAS, which is a 23-gene signature that more specifically assesses HSF1 transcriptional activity. We first identified genes that are direct transcriptional targets of HSF1 utilizing more than 40 ChIP-Seq samples in the public domain. Genes identified from ChIP-Seq were then reduced by removing genes whose expression was not altered or showed increased expression with the knockdown of HSF1. These genes were then assessed for their correlation with every other gene across 11 cancer expression datasets to develop an adjacency matrix to identify subgroups of genes that have high inter-gene correlation. The resulting 23-gene set (HAS) was then tested for its performance of assessing HSF1 activity wherein it was found to decreased when HSF1 was knocked down and increase in response to heat shock. The HAS was also able to predict outcomes of breast cancer patients that are previously observed such as high HAS was associated with worse overall survival and metastasis-free survival. This association with cancer patient outcomes extended to many other tumor types. In total, the 23-gene set we termed HAS, is an accurate tool to assess HSF1 activity from transcript expression data that is not limited to cancer-related functions of HSF1.

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Cisplatin‐induced HSF1‐HSP90 axis enhances the expression of functional PD‐L1 in oral squamous cell carcinoma

Cited by 14 publications

References 51 publications

Stress-inducible SCAN Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers

Stress-inducible SCAN Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers

Stress-Inducible SCAND Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers

HSF1 excludes CD8+ T cells from breast tumors via suppression of CCL5

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