HSP70 inhibits high glucose-induced Smad3 activation and attenuates epithelial-to-mesenchymal transition of peritoneal mesothelial cells

Li, Jun; Bao, Jinsong; Hao, Jing; Peng, Yan; Hong, Fu-Yuan

doi:10.3892/mmr.2014.2279

Cited by 19 publications

(16 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, several reports have demonstrated that HSP70 inhibits TGF-β-induced EMT by decreasing Smad2 phosphorylation [191][192][193]. Furthermore, it has been shown that HSP70 prevents high glucose-induced EMT of peritoneal mesothelial cells by inhibiting Smad3 and Smad4 phosphorylation and reactive oxygen species (ROS) production [194]. These findings suggest dual role of HSP70 in EMT, where HSP70-peptide complexes support transition of tumor cells towards acquiring mesenchymal phenotype.…”

Section: Hsp70 In Metastasismentioning

confidence: 94%

HSP70 Multi-Functionality in Cancer

Albakova

Армеев

Kanevskiy

et al. 2020

Cells

177

141

View full text Add to dashboard Cite

The 70-kDa heat shock proteins (HSP70s) are abundantly present in cancer, providing malignant cells selective advantage by suppressing multiple apoptotic pathways, regulating necrosis, bypassing cellular senescence program, interfering with tumor immunity, promoting angiogenesis and supporting metastasis. This direct involvement of HSP70 in most of the cancer hallmarks explains the phenomenon of cancer “addiction” to HSP70, tightly linking tumor survival and growth to the HSP70 expression. HSP70 operates in different states through its catalytic cycle, suggesting that it can multi-function in malignant cells in any of these states. Clinically, tumor cells intensively release HSP70 in extracellular microenvironment, resulting in diverse outcomes for patient survival. Given its clinical significance, small molecule inhibitors were developed to target different sites of the HSP70 machinery. Furthermore, several HSP70-based immunotherapy approaches were assessed in clinical trials. This review will explore different roles of HSP70 on cancer progression and emphasize the importance of understanding the flexibility of HSP70 nature for future development of anti-cancer therapies.

show abstract

Section: Hsp70 In Metastasismentioning

confidence: 94%

HSP70 Multi-Functionality in Cancer

Albakova

Армеев

Kanevskiy

et al. 2020

Cells

177

141

View full text Add to dashboard Cite

show abstract

“…Galectin-1 can also mediate high glucose peritoneal dialysis solution-induced epithelial mesenchymal transition (EMT) in human peritoneal mesothelial cells and may be a new target for the prevention and treatment of peritoneal fibrosis (Liu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

High glucose‐induced Galectin‐1 in human podocytes implicates the involvement of Galectin‐1 in diabetic nephropathy

Liu

Long²,

Fang

et al. 2014

Cell Biology International

View full text Add to dashboard Cite

The diabetic milieu is believed to change the activity, or result in damage of podocytes-a key component of the glomerular filtration barrier and known to secrete matrix for glomerular basement membrane. This in turn contributes to diabetic nephropathy. However, how podocyte dysfunction is triggered in diabetic nephropathy remains ambiguous. Galectin-1 belongs to Galectin family that bind to β-galactoside residues of glycosylated proteins. We explored whether Galectin-1 is dysregulated in diabetic nephropathy using three different techniques, namely real-time polymerase chain reaction, western blotting, and immunofluorescent staining, to follow the expression of Galectin-1 under high glucose levels in podocytes. High glucose consistently induced Galectin-1 expression. Immunohistochemistry using a Galectin-1-specific antibody also showed elevated Galectin-1 in renal tissues of diabetic patients with manifestation of nephropathy, indicating a correlation of Galectin-1 overexpression with diabetic nephropathy. Upregulation of Galectin-1 is associated with loss of podocin, which is important for the physiological function of podocytes and decreases in the renal tissues of diabetic nephropathy. Increased Galectin-1 is a causal event for the high glucose-induced loss of podocin, since silencing Galectin-1 in podocytes increased podocin expression in the presence of 25 mM glucose. Thus expression of Galectin-1 in diabetic nephropathy may serve as a marker and contribute to disease progression by interfering with podocin expression.

show abstract

“…The absence of Hsp70 in cancer cells appears to be the destruction of the Hsp70-dependent heterocomplexes of E-cadherin/catenins, which function like an anchor between neighboring cells [43]. Liu et al demonstrated that Hsp70 inhibits high-glucose-induced EMT by modulating Smad expression and activation in rat peritoneal cells [44].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells

Комарова

Marchenko

Zhakhov

et al. 2019

IJMS

View full text Add to dashboard Cite

Cancer cells are known to contain high levels of the heat shock protein 70 kDa (Hsp70), which mediates increased cell proliferation, escape from programmed cell death, enhanced invasion, and metastasis. A part of Hsp70 molecules may release from cancer cells and affect the behavior of adjacent stromal cells. To explore the effects of Hsp70 on the status of monocytes/macrophages in the tumor locale, we incubated human carcinoma cells of three distinct lines with normal and reduced content of Hsp70 with THP1 monocytes. Using two methods, we showed that the cells with knock-down of Hsp70 released a lower amount of protein in the extracellular medium. Three cycles of the co-cultivation of cancer and monocytic cells led to the secretion of several cytokines typical of the tumor microenvironment (TME) and to pro-cancer activation of the monocytes/macrophages as established by elevation of F4/80 and arginase-1 markers. Unexpectedly, the efficacy of epithelial–mesenchymal transition and resistance of carcinoma cells to anticancer drugs after incubation with monocytic cells were more pronounced in cells with lower Hsp70, e.g., releasing less Hsp70 into the extracellular milieu. These data suggest that Hsp70 released from tumor cells into the TME is able, together with the development of an anti-cancer immune response, to limit the conversion of a considerable part of monocytic cells to the pro-tumor phenotype.

show abstract

HSP70 inhibits high glucose-induced Smad3 activation and attenuates epithelial-to-mesenchymal transition of peritoneal mesothelial cells

Cited by 19 publications

References 22 publications

HSP70 Multi-Functionality in Cancer

HSP70 Multi-Functionality in Cancer

High glucose‐induced Galectin‐1 in human podocytes implicates the involvement of Galectin‐1 in diabetic nephropathy

Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells

Contact Info

Product

Resources

About