Down-regulation of HSP27 sensitizes TRAIL-resistant tumor cell to TRAIL-induced apoptosis

Zhuang, Hongqin; Jiang, Weiwei; Cheng, Wei; Qian, Keping; Dong, Wei; Cao, Lin; Huang, Qilai; Li, Shufeng; Dou, Fei; Chiu, Jen‐Fu; Fang, Xuexun; Lü, Min; Zhang, Hua

doi:10.1016/j.lungcan.2009.05.014

Cited by 47 publications

(38 citation statements)

References 69 publications

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“…HSP27 modulates thermotolerance, regulation of cell development and differentiation, as well as chaperone activity (22)(23)(24). HSP27 can also inhibit apoptosis by binding to cytochrome c and preventing its interaction with Apaf-1 and pro-caspase 9 (22).…”

Section: Discussionmentioning

confidence: 99%

HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a Smad-independent manner

et al. 2010

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Abstract. Epithelial to mesenchymal transition (EMT) isinduced by transforming growth factor-β1 (TGF-β1) and is a crucial event for cancer cells to acquire invasive and metastatic phenotypes. However, the signals that induce EMT in cancer cells have yet to be adequately defined. In this study, a proteomic investigation was performed to understand the signaling pathway of the EMT of lung cancer using two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. The protein expression profiles of A549 were compared to those of A549 cells treated with TGF-β1. Of more than 2,000 protein spots shown by 2D-DIGE, 53 were found to be up-or down-regulated upon induction with TGF-β1. In the 53 protein spots, the protein level of heat shock protein (HSP) 27 was found to increase significantly. HSP27 protein was higher in two different lung cancer cell lines, demonstrating the EMT phenomenon with TGF-β1. Notably, the silencing of HSP27 enhanced spindle integration, resulting in an additive effect with TGF-β1-induced EMT. Furthermore, the TGF-β1-induced HSP27 increase was not affected by the suppression of Smad2 and Smad3 in A549 cells. These results suggest that HSP27 was involved in TGF-β1-induced EMT in a Smad-independent manner in lung cancer cells and may provide an effective clinical strategy in lung cancer patients whose tumors are dependent on TGF-β1-induced EMT.

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Section: Discussionmentioning

confidence: 99%

HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a Smad-independent manner

et al. 2010

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“…In the meantime, HspB1 increases procaspase-3 halflife by down-regulating its degradation by the ubiquitin-proteasome machinery (Gibert et al 2012a ). Among the death receptor pathways that are under the control of HspB1 are Fas, TNFα and TRAIL (Mehlen et al 1995(Mehlen et al , 1996bZhuang et al 2009 ). In the Fas signal transduction mechanism, phosphorylated dimers of HspB1 abolished the link between activated Fas receptor and apoptotic signaling kinase1 (Ask1) by interacting with DAXX .…”

Section: Protection Against Cell Death Apoptosismentioning

confidence: 99%

Immense Cellular Implications Associated to Small Stress Proteins Expression: Impacts on Human Pathologies

Arrigo

Ducarouge

Lavial

et al. 2015

Heat Shock Proteins

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In addition to being potent chaperones that protect cells against the accumulation of unfolded proteins under stress conditions, mammalian small heat shock proteins (small Hsps) regulate many vital cellular processes in normal and pathological cells. Indeed, these Hsps are constitutively expressed in many tissues and show dramatic changes in their levels of expression in most human pathologies. They are characterized by a large spectrum of activities and are particularly active in protein conformational and infl ammatory diseases as well as in cancer pathologies. It is now believed that the immense cellular implications of small Hsps results from their ability to interact, through particular structural changes, with many different client proteins that are subsequently modulated in their activities or half-lifes. Here, we have integrated functionally and structurally the recent data in the literature concerning the interactions of mammalian small Hsps with specifi c clients. Further analysis with geneMANIA software and database confi rmed the incredibly large number of functions associated with these Hsps. The consequences for human pathologies as well as putative therapeutic strategies are discussed, particularly when the expression of small Hsps is harmful (as in some cancer pathologies) or when it appears benefi cial for patients.

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“…By inhibiting HSP27 authors could decrease the resistance of those cells to the treatment (Choi et al 2007 ). Moreover, Zhuang et al demonstrated that HSP27 inhibition sensitized A549 cancerous lung cells to apoptosis induced by TRAIL (Tumor necrosis factor-alpha-Related Apoptosis-Inducing Ligand, (Zhuang et al 2010 )). …”

Section: Hsp27: Favors Fibrosismentioning

confidence: 99%

Small Heat Shock Proteins and Fibrosis

Bellaye

Burgy

Colas

et al. 2015

Heat Shock Proteins

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Small heat shock proteins (sHSP) are involved in many essential cellular mechanisms both in physiologic and pathologic conditions. HSP27 (HSPB1), αB-crystallin (HSPB5) and HSP20 (HSPB6), the most studied members, are stressinducible chaperones with an anti-aggregation function. They have been shown to inhibit apoptosis by interacting with proteins involved in programmed cell death such as cytochrome c or caspases, to have anti-oxidant properties and/or to modulate protein homeostasis by participating in the proteasomal degradation of specifi c proteins under stress conditions. Heat shock proteins accumulate in cancer cells and this overexpression is needed for the cancer cells' survival. Accordingly, the inhibition of heat shock proteins such as HSP27 is an emerging strategy in cancer therapy (already is in phase II clinical trials). Fibrogenesis and cancer share several properties as both pathologies are characterized by genetic alterations, uncontrolled cell proliferation, altered cell interaction and communication and tissue invasion.The current review will discuss the involvement of HSP27, αB-crystallin and HSP20 in the process of fi brogenesis and in established organ fi brosis. We will dissect the impact of their function inducing the recruitment of infl ammatory cells, the

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Down-regulation of HSP27 sensitizes TRAIL-resistant tumor cell to TRAIL-induced apoptosis

Cited by 47 publications

References 69 publications

HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a Smad-independent manner

HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a Smad-independent manner

Immense Cellular Implications Associated to Small Stress Proteins Expression: Impacts on Human Pathologies

Small Heat Shock Proteins and Fibrosis

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