Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associated with tumour progression and promotes migration and invasion

Garg, Manoj; Kanojia, Deepika; Seth, Amlesh; Kumar, Rajive; Gupta, Anju; Surolia, Avadhesha; Suri, Anil

doi:10.1016/j.ejca.2009.10.020

Cited by 72 publications

(74 citation statements)

References 28 publications

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“…n.d., not determined. Notably, endogenous expression of HSP70 was already significant under basal conditions in accord with previous reports 21,22 and further induction was therefore limited. Prior to investigating combined treatment with the HSP90-inhibitor 17-AAG, we generated a dose response curve to identify appropriate concentrations for the combination experiments ( Fig.…”

Section: Combination Of Pharmacologic Hdac6 Inhibition With Further Isupporting

confidence: 73%

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

Rosik

Niegisch

Fischer

et al. 2014

Cancer Biology & Therapy

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Section: Combination Of Pharmacologic Hdac6 Inhibition With Further Isupporting

confidence: 73%

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

Rosik

Niegisch

Fischer

et al. 2014

Cancer Biology & Therapy

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“…These results were partially supported by a recent report that HSP70 depletion eradicated hepatocellular carcinoma (17), gastric cancer (3), cervical cancer (18) and bladder carcinoma (19) in mouse xenograft models. In the current study, the results from H&E staining, anti-PCNA immunohistochemical staining and the TUNEL assay obtained from these mice were consistent with in vitro results in HT29 cell lines, indicating that HSP70 shRNA possessed growth-inhibitory and apoptosis-enhancing effects on xenograft tumors in mice.…”

Section: Discussionsupporting

confidence: 78%

ShRNA-mediated gene silencing of heat shock protein 70 inhibits human colon cancer growth

Zhong

Zhang

et al. 2011

Mol Med Report

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Abstract. Heat shock protein 70 (HSP70), a chaperone involved in tumor progression, is overexpressed in various human tumors. However, its role in colon cancer progression is not completely understood. In the present study, two shRNA plasmid vectors against HSP70 were constructed and stably transfected into the colon cancer cell line HT29 to determine the effect of HSP70 on cell proliferation, cell cycle distribution and cell apoptosis in HT29 cells in vitro, and its effect on xenograft tumor growth and apoptosis in vivo. Cell proliferation was determined using MTT assay. The results revealed that HSP70 silencing efficiently inhibited the growth of HT29 cells in culture, induced cell cycle arrest at the G1 phase, and significantly increased apoptosis. Moreover, stable clones from the HSP70 shRNA-2 vector suppressed xenograft tumor growth and enhanced apoptosis in vivo compared with a mock and vector control group. In conclusion, specific HSP70 shRNA silencing may inhibit colon cancer growth, indicating that HSP70 silencing is a potential therapeutic strategy for the treatment of colon cancer. IntroductionColorectal carcinoma (CRC) is one of the most common malignant diseases in China. The incidence of colon cancer has been on the increase, becoming a major threat to public health. CRC is the third most frequently diagnosed cancer in the USA. In 2005, an estimated 105,950 new cases of colon cancer occurred. During the same year, an esti mated 55,290 individuals succumbed to CRC (1). Therefore, it is vital that early detection and treatment be improved, particularly the efficacy of treatment to reduce mortality and extend the lives of patients.Heat shock proteins (HSP), which are stress proteins acting as molecular chaperones, are generally induced by various environmental and pathophysiological stimuli (2). The protective function of HSP70 is related to its ability to promote folding of nascent polypeptides and to remove denatured proteins (3). However, HSP70 facilitates cancer cell survival and growth in various human tumor cells by inhibiting apoptosis and promoting proliferation (4,5). The specific expression of HSP70 acting as an anti-apoptotic chaperone protein is commonly higher in cancer cells including breast, colon (6), ovarian (6) and pancreatic cancers (7). An elevated expression of HSP70 correlates with increased tumor cell proliferation, invasion, migration and poor prognosis. Therefore, HSP70 has been proposed as a putative target for cancer treatment.RNA interference (RNAi), a genetic interference phenomenon that involves the post-transcriptional gene silencing mechanism, effectively suppresses the expression of a particular gene through the introduction of short interfering RNAs (8). However, the effect of down-regulated HSP70 expression by RNAi on colon cancer growth in vitro and in vivo has yet to be examined.In this study, two shRNA plasmid vectors against HSP70 were constructed and transfected into the colon cancer cell line HT29 using RNAi technology, which persistently generated siRNA inside...

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“…HSP70 is often overexpressed in tumor cells, and evidence suggests that its overexpression contributes to tumorigenesis (Calderwood et al, 2006;Mosser and Morimoto, 2004). In the case of bladder cancer, overexpression of the testis-specific protein HSP70-2 was 2372 Journal of Cell Science 124 (14) associated with increased malignancy because specific knockdown resulted in reduced migration and invasion abilities in vitro and suppressed tumor growth in a xenograft assay (Garg et al, 2010). Clinically, hyperthermia increases cancer patient survival when used in combination with radiation or chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of HSP70 inhibits cofilin phosphorylation and promotes lymphocyte migration in heat-stressed cells

Simard

Reynolds

Kraguljac

et al. 2011

Journal of Cell Science

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Hyperthermia adversely affects cell structure and function, but also induces adaptive responses that allow cells to tolerate these stressful conditions. For example, heat-induced expression of the molecular chaperone protein HSP70 can prevent stress-induced cell death by inhibiting signaling pathways that lead to apoptosis. In this study, we used high-resolution two-dimensional gel electrophoresis and phosphoprotein staining to identify signaling pathways that are altered by hyperthermia and modulated by HSP70 expression. We found that in heat-shocked cells, the actin-severing protein cofilin acquires inhibitory Ser3 phosphorylation, which is associated with an inhibition of chemokine-stimulated cell migration. Cofilin phosphorylation appeared to occur as a result of the heat-induced insolubilization of the cofilin phosphatase slingshot (SSH1-L). Overexpression of HSP70 reduced the extent of SSH1-L insolubilization and accelerated its resolubilization when cells were returned to 37°C after exposure to hyperthermia, resulting in a more rapid dephosphorylation of cofilin. Cells overexpressing HSP70 also had an increased ability to undergo chemotaxis following exposure to hyperthermia. These results identify a critical heat-sensitive target controlling cell migration that is regulated by HSP70 and point to a role for HSP70 in immune cell functions that depend upon the proper control of actin dynamics.

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Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associated with tumour progression and promotes migration and invasion

Cited by 72 publications

References 28 publications

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

ShRNA-mediated gene silencing of heat shock protein 70 inhibits human colon cancer growth

Overexpression of HSP70 inhibits cofilin phosphorylation and promotes lymphocyte migration in heat-stressed cells

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