HSPA2 Chaperone Contributes to the Maintenance of Epithelial Phenotype of Human Bronchial Epithelial Cells but Has Non-Essential Role in Supporting Malignant Features of Non-Small Cell Lung Carcinoma, MCF7, and HeLa Cancer Cells

Sojka, Damian Robert; Gogler-Pigłowska, Agnieszka; Klarzyńska, Katarzyna; Klimczak, Marta; Żylicz, Maciej; Głowala-Kosińska, Magdalena; Krawczyk, Z; Ścieglińska, Dorota

doi:10.3390/cancers12102749

Cited by 4 publications

(4 citation statements)

References 57 publications

(118 reference statements)

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“…The cell lines produced comparable levels of HSPA1 (Figure S3). Both models were described in detail in our previous papers [21,26,27], where we found modulation of HSPA1 or HSPA2 expression levels had no effect on proliferation of NSCLC cells [21,26].…”

Section: Hspa1 Exerts Very Limited Cell Type-dependent Protection Against Ma Toxicity While the Role Of Hspa2 In Cytoprotection Is Negligmentioning

confidence: 83%

“…However, the expression of several other HSPA genes, due to a lack of the HSE sequence, cannot be elevated in a HSF1-dependent manner. An exemplary representative is HSPA2, the gene coding for a testis-enriched chaperone with a critical role for spermatogenesis [19] but also implicated in modulating the phenotype and differentiation of epithelial cells [20,21]. The knowledge about the contribution of HSPA2 to the cytoprotective system of the cells has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A

Sojka

Hasterok

Vydra

et al. 2021

Cells

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Manumycin A (MA) is a well-tolerated natural antibiotic showing pleiotropic anticancer effects in various preclinical in vitro and in vivo models. Anticancer drugs may themselves act as stressors to induce the cellular adaptive mechanism that can minimize their cytotoxicity. Heat shock proteins (HSPs) as cytoprotective factors can counteract the deleterious effects of various stressful stimuli. In this study, we examined whether the anticancer effects of MA can be counteracted by the mechanism related to HSPs belonging to the HSPA (HSP70) family. We found that MA caused cell type-specific alterations in the levels of HSPAs. These changes included concomitant upregulation of the stress-inducible (HSPA1 and HSPA6) and downregulation of the non-stress-inducible (HSPA2) paralogs. However, neither HSPA1 nor HSPA2 were necessary to provide protection against MA in lung cancer cells. Conversely, the simultaneous repression of several HSPA paralogs using pan-HSPA inhibitors (VER-155008 or JG-98) sensitized cancer cells to MA. We also observed that genetic ablation of the heat shock factor 1 (HSF1) transcription factor, a main transactivator of HSPAs expression, sensitized MCF7 cells to MA treatment. Our study reveals that inhibition of HSF1-mediated heat shock response (HSR) can improve the anticancer effect of MA. These observations suggest that targeting the HSR- or HSPA-mediated adaptive mechanisms may be a promising strategy for further preclinical developments.

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Section: Hspa1 Exerts Very Limited Cell Type-dependent Protection Against Ma Toxicity While the Role Of Hspa2 In Cytoprotection Is Negligmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A

Sojka

Hasterok

Vydra

et al. 2021

Cells

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“…Of note, however, and contrary to above cited studies, is that Soika et al [ 111 ] did not observe any effects of knockdown of HSP70-2 on cell growth, migration, adhesion, and invasion of MCF-7 cells. Yet, a recent study of Yang et al [ 112 ] supported the essential role of HSP70-2 in tumorigenesis.…”

Section: Role Of Other Hsp70 Subfamily Members In Tumorigenesismentioning

confidence: 65%

HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy

Kabakov

Gabai²

2021

Cells

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The high frequency of breast cancer worldwide and the high mortality among women with this malignancy are a serious challenge for modern medicine. A deeper understanding of the mechanisms of carcinogenesis and emergence of metastatic, therapy-resistant breast cancers would help development of novel approaches to better treatment of this disease. The review is dedicated to the role of members of the heat shock protein 70 subfamily (HSP70s or HSPA), mainly inducible HSP70, glucose-regulated protein 78 (GRP78 or HSPA5) and GRP75 (HSPA9 or mortalin), in the development and pathogenesis of breast cancer. Various HSP70-mediated cellular mechanisms and pathways which contribute to the oncogenic transformation of mammary gland epithelium are reviewed, as well as their role in the development of human breast carcinomas with invasive, metastatic traits along with the resistance to host immunity and conventional therapeutics. Additionally, intracellular and cell surface HSP70s are considered as potential targets for therapy or sensitization of breast cancer. We also discuss a clinical implication of Hsp70s and approaches to targeting breast cancer with gene vectors or nanoparticles downregulating HSP70s, natural or synthetic (small molecule) inhibitors of HSP70s, HSP70-binding antibodies, HSP70-derived peptides, and HSP70-based vaccines.

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“…The CRISPR/Cas9-modified cell lines were generated as described previously 29 . Briefly, NCI-H1299 cells were transfected with HSPA2 Double Nickase Plasmid (sc-400832-NIC, Santa Cruz Biotechnology, Inc., Dallas, TX, USA) and Control Double Nickase Plasmid (sc-437281, Santa Cruz Biotechnology).…”

Section: Generation Of Modified Cell Linesmentioning

confidence: 99%

Heat shock protein A2 is a novel extracellular vesicle-associated protein

Sojka

Abramowicz

Adamiec-Organiściok

et al. 2023

Sci Rep

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Abstract70-kDa Heat Shock Proteins (HSPA/HSP70) are chaperones playing a central role in the proteostasis control mechanisms. Their basal expression can be highly elevated as an adaptive response to environmental and pathophysiological stress conditions. HSPA2, one of poorly characterised chaperones of the HSPA/HSP70 family, has recently emerged as epithelial cells differentiation-related factor. It is also commonly expressed in cancer cells, where its functional significance remains unclear. Previously, we have found that proteotoxic stress provokes a decrease in HSPA2 levels in cancer cells. In the present study we found that proteasome inhibition-related loss of HSPA2 from cancer cells neither is related to a block in the gene transcription nor does it relate to increased autophagy-mediated disposals of the protein. Proteotoxic stress stimulated extracellular release of HSPA2 in extracellular vesicles (EVs). Interestingly, EVs containing HSPA2 are also released by non-stressed cancer and normal cells. In human urinary EVs levels of HSPA2 were correlated with the levels of TSG101, one of the main EVs markers. We conclude that HSPA2 may constitute basic components of EVs. Nevertheless, its specific role in EVs and cell-to-cell communication requires further investigation.

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HSPA2 Chaperone Contributes to the Maintenance of Epithelial Phenotype of Human Bronchial Epithelial Cells but Has Non-Essential Role in Supporting Malignant Features of Non-Small Cell Lung Carcinoma, MCF7, and HeLa Cancer Cells

Cited by 4 publications

References 57 publications

Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A

Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A

HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy

Heat shock protein A2 is a novel extracellular vesicle-associated protein

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