Role of HSP70 in response to (thermo)radiotherapy: analysis of gene expression in canine osteosarcoma cells by RNA-seq

Nytko, Katarzyna J.; Thumser-Henner, Pauline; Russo, Giancarlo; Weyland, Mathias S.; Bley, Carla Rohrer

doi:10.1038/s41598-020-69619-2

Cited by 8 publications

(6 citation statements)

References 34 publications

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“…Indeed, Glembatumumab Vedotin has been used in the context of Osteosarcoma with some degree of ant-tumor activity [71]. Recently, GPNMB was shown to be the most upregulated gene in osteosarcoma cells following HSP70 knockdown [72]. Thus, combining broad specificity HSP inhibitors with Glembatumumab Vedotin may prove effective in many solid cancer indications.…”

Section: Discussionmentioning

confidence: 99%

HSP90 inhibitors induce GPNMB cell-surface expression by modulating lysosomal positioning and sensitize breast cancer cells to glembatumumab vedotin

et al. 2022

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Transmembrane glycoprotein NMB (GPNMB) is a prognostic marker of poor outcome in patients with triple-negative breast cancer (TNBC). Glembatumumab Vedotin, an antibody drug conjugate targeting GPNMB, exhibits variable efficacy against GPNMB-positive metastatic TNBC as a single agent. We show that GPNMB levels increase in response to standard-of-care and experimental therapies for multiple breast cancer subtypes. While these therapeutic stressors induce GPNMB expression through differential engagement of the MiTF family of transcription factors, not all are capable of increasing GPNMB cell-surface localization required for Glembatumumab Vedotin inhibition. Using a FACS-based genetic screen, we discovered that suppression of heat shock protein 90 (HSP90) concomitantly increases GPNMB expression and cell-surface localization. Mechanistically, HSP90 inhibition resulted in lysosomal dispersion towards the cell periphery and fusion with the plasma membrane, which delivers GPNMB to the cell surface. Finally, treatment with HSP90 inhibitors sensitizes breast cancers to Glembatumumab Vedotin in vivo, suggesting that combination of HSP90 inhibitors and Glembatumumab Vedotin may be a viable treatment strategy for patients with metastatic TNBC.

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Section: Discussionmentioning

confidence: 99%

HSP90 inhibitors induce GPNMB cell-surface expression by modulating lysosomal positioning and sensitize breast cancer cells to glembatumumab vedotin

et al. 2022

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“…In experiments using radioresistant lung cancer cells, a knockdown of HSF1 and administration of an HSP90 inhibitor resulted in a high level of cell apoptosis and increased cell sensitivity to radiotherapy [103]. Apart from these positive effects, the inhibition of HSP90 induces the release of HSF1 from the HSP90 complex, thereby stimulating the transcription of the cytoprotective chaperones HSP70 and HSP27 [8,42,104]. Therefore, this forms a feedback loop to counteract the effect of HSP90 inhibition.…”

Section: Hsf1 In Therapeutic Resistancementioning

confidence: 99%

Heat Shock Factor 1 Inhibition: A Novel Anti-Cancer Strategy with Promise for Precision Oncology

Gumilar,

Chin,

Ibrahim

et al. 2023

Cancers

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Heat shock factor 1 (HSF1) is a transcription factor crucial for regulating heat shock response (HSR), one of the significant cellular protective mechanisms. When cells are exposed to proteotoxic stress, HSF1 induces the expression of heat shock proteins (HSPs) to act as chaperones, correcting the protein-folding process and maintaining proteostasis. In addition to its role in HSR, HSF1 is overexpressed in multiple cancer cells, where its activation promotes malignancy and leads to poor prognosis. The mechanisms of HSF1-induced tumorigenesis are complex and involve diverse signaling pathways, dependent on cancer type. With its important roles in tumorigenesis and tumor progression, targeting HSF1 offers a novel cancer treatment strategy. In this article, we examine the basic function of HSF1 and its regulatory mechanisms, focus on the mechanisms involved in HSF1′s roles in different cancer types, and examine current HSF1 inhibitors as novel therapeutics to treat cancers.

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“…Mmp1 is the most significantly downregulated gene in Hsp70 knockdown canine OSA cells, and increased expression of mmp2 and mmp9 was linked to increased invasive capability in canine OSA ( 78 , 148 , 149 ).…”

Section: Response To Ecm Environment and Cell Adhesionmentioning

confidence: 99%

An Update on Molecular Pathways Regulating Vasculogenic Mimicry in Human Osteosarcoma and Their Role in Canine Oncology

et al. 2021

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Canine tumors are valuable comparative models for human counterparts, especially to explore novel biomarkers and to understand pathways and processes involved in metastasis. Vasculogenic mimicry (VM) is a unique property of malignant cancer cells which promote metastasis. Thus, it represents an opportunity to investigate both the molecular mechanisms and the therapeutic targets of a crucial phenotypic malignant switch. Although this biological process has been largely investigated in different human cancer types, including osteosarcoma, it is still largely unknown in veterinary pathology, where it has been mainly explored in canine mammary tumors. The presence of VM in human osteosarcoma is associated with poor clinical outcome, reduced patient survival, and increased risk of metastasis and it shares the main pathways involved in other type of human tumors. This review illustrates the main findings concerning the VM process in human osteosarcoma, search for the related current knowledge in canine pathology and oncology, and potential involvement of multiple pathways in VM formation, in order to provide a basis for future investigations on VM in canine tumors.

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Role of HSP70 in response to (thermo)radiotherapy: analysis of gene expression in canine osteosarcoma cells by RNA-seq

Cited by 8 publications

References 34 publications

HSP90 inhibitors induce GPNMB cell-surface expression by modulating lysosomal positioning and sensitize breast cancer cells to glembatumumab vedotin

HSP90 inhibitors induce GPNMB cell-surface expression by modulating lysosomal positioning and sensitize breast cancer cells to glembatumumab vedotin

Heat Shock Factor 1 Inhibition: A Novel Anti-Cancer Strategy with Promise for Precision Oncology

An Update on Molecular Pathways Regulating Vasculogenic Mimicry in Human Osteosarcoma and Their Role in Canine Oncology

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