Heat shock protein 70–2 (HSP70-2) is a novel therapeutic target for colorectal cancer and is associated with tumor growth

Abstract

BackgroundColorectal cancer (CRC) is the third leading cause of cancer related deaths worldwide both in men and women. Our recent studies have indicated an association of heat shock protein 70–2 (HSP70-2) with bladder urothelial carcinoma. In the present study, we investigated the association of HSP70-2 with various malignant properties of colorectal cancer cells and clinic-pathological features of CRC in clinical specimens.MethodsHSP70-2 mRNA and protein was investigated expression by RT-PCR, immunohistochemistry, immunofluorescence, flow cytometry and Western blotting in CRC clinical specimens and COLO205 and HCT116 cell lines. Plasmid-based gene silencing approach was employed to study the association of HSP70-2 with various malignant properties of COLO205 and HCT116 cells in in vitro and with tumor progression in in vivo COLO205 human xenograft mice model.ResultsHSP70-2 expression was detected in 78 % of CRC patients irrespective of various stages and grades by RT-PCR and IHC. Our analysis further revealed that HSP70-2 expression was detected in both COLO205 and HCT116 cell lines. Ablation of HSP70-2 expression resulted in reduced cellular growth, colony forming ability, migratory and invasive ability of CRC cells. In addition, ablation of HSP70-2 expression showed significant reduction in tumor growth in COLO205 human xenograft in in vivo mouse model.ConclusionCollectively, our results indicate that HSP70-2 is associated with CRC clinical specimens. In addition, down regulation of HSP70-2 expression reduces cellular proliferation and tumor growth indicating that HSP70-2 may be a potential therapeutic target for CRC treatment.

Hepatitis B virus‐regulated growth of liver cancer cells occurs through the microRNA‐340‐5p‐activating transcription factor 7‐heat shock protein A member 1B axis

“…Heat shock proteins (HSP) are stress‐inducible molecules that modulate cellular responses to conditions such as chronic inflammation, fibrosis, and carcinogenesis. Notably, HSPA1B (also referred to as HSP70‐2), a member of the HSP family, had been shown to promote cell proliferation, migration, and invasion and to suppress apoptosis in various cancers . Elevated expression of HSPA1B was also reported in HCC tissue and had been shown to play a role in HBV‐related HCC development .…”

“…Notably, HSPA1B (also referred to as HSP70-2), a member of the HSP family, had been shown to promote cell proliferation, migration, and invasion and to suppress apoptosis in various cancers. 17,18 Elevated expression of HSPA1B was also reported in HCC tissue and had been shown to play a role in HBV-related HCC development. 19 We therefore further investigated the functional role of HSPA1B in HCC by silencing endogenous HSPA1B expression using siRNA (si-HSP).…”

Molecular pathway analysis indicates a distinct metabolic and immune phenotype in women with right-sided colon cancer

“…All the genes from our datasets that were linked through this pathway were upregulated, suggesting an increase in activity in this pathway; heat shock protein ( HSP ) 70 , hypoxia up-regulated protein 1 ( HYOU1 ), and CHIP partake in antigen endocytosis, antigen presentation, and T-cell immune response. Of note, the protein encoded by HYOU1 belongs to the HSP70 family, which has been shown to be related to cell growth and cancer progression (Jagadish et al, 2016). Interestingly, HSP105 , a member of the HSP70 family that has been shown to play a role in anti-tumor immune response, was downregulated (Miyazaki et al, 2005; Yokomine et al, 2006; Yokomine et al, 2007).…”

“…These proteins are also involved in immune response. Upregulation of HSP70 expression has been shown to increase cell proliferation and tumor growth, and has been associated with poorer prognosis in colon cancer (Jagadish et al, 2016). HSP105 partakes in increasing anti-tumor immune response, which was downregulated in RCC (Miyazaki et al, 2005; Jagadish et al, 2016).…”

“…Upregulation of HSP70 expression has been shown to increase cell proliferation and tumor growth, and has been associated with poorer prognosis in colon cancer (Jagadish et al, 2016). HSP105 partakes in increasing anti-tumor immune response, which was downregulated in RCC (Miyazaki et al, 2005; Jagadish et al, 2016). Our findings of the dysregulation of these heat shock proteins in women with RCC versus LCC may play a role in the more aggressive nature and generally poorer prognosis of RCC.…”