Functional redundancy of HSPA1, HSPA2 and other HSPA proteins in non-small cell lung carcinoma (NSCLC); an implication for NSCLC treatment
| Autor: | Agnieszka Gogler-Pigłowska, Natalia Vydra, Zdzisław Krawczyk, Damian Robert Sojka, Alexander Jorge Cortez, Piotr Filipczak, Dorota Scieglinska |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Lung Neoplasms
Science Cell HSP72 Heat-Shock Proteins Biology Article Heat shock protein Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Carcinoma Humans HSP70 Heat-Shock Proteins Cell Proliferation Gene knockdown Multidisciplinary Bortezomib Cancer medicine.disease respiratory tract diseases Cancer therapeutic resistance Proteostasis medicine.anatomical_structure Proteasome Drug Resistance Neoplasm Gene Knockdown Techniques Cancer research Medicine Cisplatin Non-small-cell lung cancer medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-15 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Heat shock proteins (HSPs) are a large group of chaperones considered critical for maintaining cellular proteostasis. Their aberrant expression in tumors can modulate the course of processes defined as hallmarks of cancer. Previously, we showed that both stress-inducible HSPA1 and testis-enriched HSPA2, highly homologous members of the HSPA (HSP70) family, are often overexpressed in non-small cell lung carcinoma (NSCLC). HSPA1 is among the best characterized cancer-related chaperones, while the significance of HSPA2 for cancer remains poorly understood. Previously we found that in primary NSCLC, HSPA1 was associated with good prognosis while HSPA2 correlated with bad prognosis, suggesting possible different roles of these proteins in cancer. Therefore, in this work we investigated the impact of HSPA1 and HSPA2 on NSCLC cell phenotype. We found that neither paralog-selective nor simultaneous knockdown of HSPA1 and HSPA2 gene expression reduced growth and chemoresistance of NSCLC cells. Only blocking of HSPA proteins using pan-HSPA inhibitors, VER-155008 or JG-98, exerted potent anticancer effect on NSCLC cells, albeit the final outcome was cell type-dependent. Pan-HSPA inhibition sensitized NSCLC cells to bortezomib, but not to platinum derivates. Our result suggests the inhibitors of proteasome and HSPAs seem an effective drug combination for pre-clinical development in highly aggressive NSCLC. |
| Databáze: | OpenAIRE |
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