Hsp70 and gama-Semino protein as possible prognostic marker of prostate cancer

Kumar, Sanjay; Gurshaney, Sanjeev; Adagunodo, Yori; Gage, Erica; Qadri, Shezreen; Sharma, Mahak; Malik, Shalie; Manne, Upender; Singh, Udai P.; Singh, Rajesh; Mishra, Manoj K.

doi:10.2741/4684

Cited by 12 publications

(2 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HSP70, a member of the evolutionarily highly conserved heat shock protein family, plays an important role in enhancing cell resistance to various stimuli and alleviating cell damage via its molecular chaperone function in protein folding, unfolding, and disaggregation (26). Lines of studies have revealed that the basal level of HSP70 was high in several types of malignancies (27)(28)(29)(30)(31) and that it has been categorized as a bad prognosis factor (27,28). HSP70 has also been demonstrated to cooperate in chemotherapy and radiotherapy resistance probably due to its capacity to disable cell death (32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 Promotes Gastric Cancer Metastasis and Suppresses Apoptosis by Facilitating MAPK Signaling Pathway Through HSP70 Up-Regulation

Fang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

ObjectiveTo examine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on gastric cancer (GC) progression and prognosis, and to explore the underlying mechanism.MethodsPCSK9 expression levels in human GC tissues were determined by quantitative real-time PCR, western blotting, and immunohistochemical assay. PCSK9 serum levels were detected by enzyme-linked immunosorbent assay. The relationships of PCSK9 and GC progression and survival were analyzed using the Chi-square test, Kaplan-Meier analysis, and Cox proportional hazards model. The effect of PCSK9 on cell invasion, migration, and apoptosis were determined in human GC cell lines and mouse xenograft model separately using PCSK9 knockdown and overexpression strategies. The PCSK9 interacting molecules, screened by co-immunoprecipitation combined with LC-MS/MS, were identified by immunofluorescence localization and western blotting. Additionally, the mitogen-activated protein kinase (MAPK) pathway was assessed by western blotting.ResultsPCSK9 mRNA and protein levels were significantly elevated in GC tissues compared with the paired normal tissues at our medical center (P < 0.001). Notably, the up-regulation of PCSK9 expression in GC tissues was related to tumor progression and poor survival. GC patients had higher serum levels of PCSK9 than the age-matched healthy controls (P < 0.001); PCSK9 promoted invasive and migratory ability and inhibited apoptosis in GC cells with no apparent affection in cell proliferation. The silencing of PCSK9 reversed these effects, suppressing tumor metastasis in vitro and in vivo. Furthermore, PCSK9 maintained these functions through up-regulating heat shock protein 70 (HSP70), ultimately facilitating the mitogen-activated protein kinase (MAPK) pathway.ConclusionCollectively, our data revealed that high PCSK9 expression levels in GC tissue were correlated with GC progression and poor prognosis and that PCSK9 could promote GC metastasis and suppress apoptosis by facilitating MAPK signaling pathway through HSP70 up-regulation. PCSK9 may represent a novel potential therapeutic target in GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 Promotes Gastric Cancer Metastasis and Suppresses Apoptosis by Facilitating MAPK Signaling Pathway Through HSP70 Up-Regulation

Fang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…This may not only be due to decreased pro-apoptotic activity resulting from lower Axud1 levels in mammals, but also to increased hsp70 expression at levels that foster cell survival. Likewise, this relation (lower Axud1 expression and higher Hsp70 levels) has been independently documented in multiple studies, being related to progression and poor prognosis for prostate cancer [ 49 , 50 ], lung squamous cell carcinoma [ 19 , 51 ], and hepatocellular carcinoma [ 14 , 52 ]. In any case, this relationship between low levels of Axud1 and high levels of Hsp70 in the progression and aggressiveness of cancers must be confirmed in studies conducted for this purpose.…”

Section: Discussionmentioning

confidence: 93%

Drosophila DAxud1 Has a Repressive Transcription Activity on Hsp70 and Other Heat Shock Genes

Zúñiga-Hernández

Meneses

Bastías

et al. 2023

IJMS

View full text Add to dashboard Cite

Drosophila melanogaster DAxud1 is a transcription factor that belongs to the Cysteine Serine Rich Nuclear Protein (CSRNP) family, conserved in metazoans, with a transcriptional transactivation activity. According to previous studies, this protein promotes apoptosis and Wnt signaling-mediated neural crest differentiation in vertebrates. However, no analysis has been conducted to determine what other genes it might control, especially in connection with cell survival and apoptosis. To partly answer this question, this work analyzes the role of Drosophila DAxud1 using Targeted-DamID-seq (TaDa-seq), which allows whole genome screening to determine in which regions it is most frequently found. This analysis confirmed the presence of DAxud1 in groups of pro-apoptotic and Wnt pathway genes, as previously described; furthermore, stress resistance genes that coding heat shock protein (HSP) family genes were found as hsp70, hsp67, and hsp26. The enrichment of DAxud1 also identified a DNA-binding motif (AYATACATAYATA) that is frequently found in the promoters of these genes. Surprisingly, the following analyses demonstrated that DAxud1 exerts a repressive role on these genes, which are necessary for cell survival. This is coupled with the pro-apoptotic and cell cycle arrest roles of DAxud1, in which repression of hsp70 complements the maintenance of tissue homeostasis through cell survival modulation.

show abstract

Hsp70‐Targeting and Size‐Tunable Nanoparticles Combine with PD‐1 Checkpoint Blockade to Treat Glioma

Xie

Wang

Tong

et al. 2023

Small

View full text Add to dashboard Cite

Invasive glioma usually disrupts the integrity of the blood‐brain barrier (BBB), making the delivery of nanodrugs across the BBB possible, but sufficient targeting ability is still avidly needed to improve drug accumulation in glioma. Membrane‐bound heat shock protein 70 (Hsp70) is expressed on the membrane of glioma cells rather than adjacent normal cells, therefore it can serve as a specific glioma target. Meanwhile, prolonging the retention in tumors is important for active‐targeting nanoparticles to overcome receptor‐binding barriers. Herein, the Hsp70‐targeting and acid‐triggered self‐assembled gold nanoparticles (D‐A‐DA/TPP) are proposed to realize selective delivery of doxorubicin (DOX) to glioma. In the weakly acidic glioma matrix, D‐A‐DA/TPP formed aggregates to prolong retention, improve receptor‐binding efficiency and facilitate acid‐responsive DOX release. DOX accumulation in glioma induced immunogenic cell death (ICD) to promote antigen presentation. Meanwhile, combination with the PD‐1 checkpoint blockade further activate T cells and provokes robust anti‐tumor immunity. The results showed that D‐A‐DA/TPP can induce more glioma apoptosis. Furthermore, in vivo studies indicated D‐A‐DA/TPP plus PD‐1 checkpoint blockade significantly improved median survival time. This study offeres a potential nanocarrier combining size‐tunable strategy with active targeting ability to increase drug enrichment in glioma and synergizes with PD‐1 checkpoint blockade to achieve chemo‐immunotherapy.

show abstract

Hsp70 and gama-Semino protein as possible prognostic marker of prostate cancer

Cited by 12 publications

References 82 publications

Proprotein Convertase Subtilisin/Kexin Type 9 Promotes Gastric Cancer Metastasis and Suppresses Apoptosis by Facilitating MAPK Signaling Pathway Through HSP70 Up-Regulation

Proprotein Convertase Subtilisin/Kexin Type 9 Promotes Gastric Cancer Metastasis and Suppresses Apoptosis by Facilitating MAPK Signaling Pathway Through HSP70 Up-Regulation

Drosophila DAxud1 Has a Repressive Transcription Activity on Hsp70 and Other Heat Shock Genes

Hsp70‐Targeting and Size‐Tunable Nanoparticles Combine with PD‐1 Checkpoint Blockade to Treat Glioma

Contact Info

Product

Resources

About