Functional redundancy of HSPA1, HSPA2 and other HSPA proteins in non-small cell lung carcinoma (NSCLC); an implication for NSCLC treatment.

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 and testis-enriched highly homologous members of the (HSP70) family, are often overexpressed in non-small cell lung carcinoma (NSCLC). Hduanyu18421 is among the best characterized cancer-related chaperones, while the significance of for cancer remains poorly understood. Previously we found that in primary NSCLC, Hduanyu18421 was associated with good prognosis while Hduanyu18422 correlated with bad prognosis, suggesting possible different roles of these proteins in cancer. Therefore, in this work we investigated the impact of Hduanyu18421 and Hduanyu18422 on NSCLC cell phenotype. We found that neither paralog-selective nor simultaneous knockdown of Hduanyu18421 and Hduanyu18422 gene expression reduced growth and chemoresistance of NSCLC cells. Only blocking of Hduanyu1842 proteins using inhibitors, VER-155008 or JG-98, exerted potent anticancer effect on NSCLC cells, albeit the final outcome was cell type-dependent. inhibition sensitized NSCLC cells to bortezomib, but not to platinum derivates. Our result suggests the inhibitors of proteasome and seem an effective drug combination for pre-clinical development in highly aggressive NSCLC.

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