Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer.

@article{Daugaard2007LensEG,
  title={Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer.},
  author={Mads Daugaard and Thomas Kirkegaard-S{\o}rensen and Marie Stampe Ostenfeld and Mads Aaboe and Maria H{\o}yer-Hansen and Torben Falck Orntoft and Mikkel Rohde and Marja J{\"a}{\"a}ttel{\"a}},
  journal={Cancer research},
  year={2007},
  volume={67 6},
  pages={
          2559-67
        }
}
Heat shock protein 70-2 (Hsp70-2) is a chaperone protein essential for the growth of spermatocytes and cancer cells. Here, we show that Hsp70-2 depletion triggers lysosomal membrane permeabilization and cathepsin-dependent cell death and identify lens epithelium-derived growth factor (LEDGF) as an Hsp70-2-regulated guardian of lysosomal stability in human cancer. Knockdown of LEDGF in cancer cells induces destabilization of lysosomal membranes followed by caspase-independent and Bcl-2-resistant… 
View on PubMed
cancerres.aacrjournals.org
119 Citations
Highly Influential Citations
11
Background Citations
64
Methods Citations
3
Results Citations
4

Figures from this paper

119 Citations

Citation Type

Citation Type

Heat Shock Protein Hsp72 Controls Oncogene-Induced Senescence Pathways in Cancer Cells
TLDR
It is demonstrated that the p53-dependent pathway controlled by Hsp72 depends on the oncogenic form of phosphatidylinositol 3-kinase (PI3K), which explains why cancer cells become “addicted” to this heat shock protein.
HSP70s: From Tumor Transformation to Cancer Therapy
TLDR
This review lays out recent advances in the HSP70s-mediated cancer diagnosis and therapy and would be enlightening for clinical cancer medicine.
BAMLET Activates a Lysosomal Cell Death Program in Cancer Cells
TLDR
Data indicate that BAMLET triggers lysosomal cell death pathway in cancer cells, thereby clarifying the ability of α-lactalbumin:oleate complexes to kill highly apoptosis-resistant tumor cells.
HSP70 Multi-Functionality in Cancer
TLDR
Different roles of HSP70 on cancer progression are explored and the importance of understanding the flexibility of H SP70 nature for future development of anti-cancer therapies is emphasized.
LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer
TLDR
The results suggest that LEDGF/p75 is not an inhibitor of apoptosis but rather an antagonist of oxidative stress-induced necrosis, and that its overexpression in PCa leads to ERp57 upregulation.
Expression of the Stress Response Oncoprotein LEDGF/p75 in Human Cancer: A Study of 21 Tumor Types
TLDR
Elevated transcript or protein expression of LEDGF/p75 was observed in several tumor types, and a rationale for ongoing studies aimed at understanding the clinical significance of its expression in specific human cancers is provided.
Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75
TLDR
The results underscore the ability of docetaxel to induce concomitantly caspase-dependent and independent death pathways in prostate cancer cells and point to LEDGF/p75 as a potential contributor to cellular resistance to docetxel-induced lysosomal destabilization and cell death, and an attractive candidate for molecular targeting in HRPC.
Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes in autophagy-mediated proteolysis in human retinal pigment epithelial cells
TLDR
The molecular chaperone Hsp70, proteasomes and autophagy have an important regulatory role in the protein turnover of human RPE cells and may thus open new avenues for understanding degenerative processes in retinal cells.
Inducible HSP70 Antagonizes IL-1β Cytocidal Effects through Inhibiting NF-kB Activation via Destabilizing TAK1 in HeLa Cells
TLDR
Evidence is provided for a novel signaling mechanism involving HSP70, TAK1, and NF-κB in the response of IL-1β cytocidal effects and insight into mechanisms by which H SP70 exerts its cytoprotective action upon toxic stimuli in tumor cells is provided.
HSP70–eIF4G Interaction Promotes Protein Synthesis and Cell Proliferation in Hepatocellular Carcinoma
TLDR
It is demonstrated that HSP70 expression is positively correlated with eIF4G in tumor specimens from 25 HCC patients, in contrast to the adjacent non-tumorous tissues, and that both influence the survival of H CC patients.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 54 REFERENCES
Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2.
TLDR
Results show that tumorigenic breast cancer cells depend on the constitutive high expression of Hsp70 to suppress a transformation-associated death program, which may open new possibilities for treatment of cancers that have acquired resistance to therapies activating the classical apoptosis pathway.
Heat Shock Protein 70 Promotes Cell Survival by Inhibiting Lysosomal Membrane Permeabilization
TLDR
Data identify Hsp70 as the first survival protein that functions by inhibiting the death-associated permeabilization of lysosomes, and shows that it is physically associated with the membranes.
Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms.
TLDR
The first thorough analysis of the expression and function of the cytosolic Hsp70 proteins in human cancer cells is presented and HSp70-2 is identified, a protein essential for spermatogenesis, as an important regulator of cancer cell growth.
Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress.
TLDR
Siramesine, a novel sigma-2 receptor ligand, effectively induces caspase-independent programmed cell death in immortalized and transformed cells of various origins and is presented as a promising new drug for the treatment of tumors resistant to traditional therapies.
Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes.
TLDR
Findings show Hsp70 to rescue melanocytes from UVB induced apoptosis by preventing release of cathepsins from lysosomes, Bax translocation and cytochrome c release from mitochondria.
Human bcl-2 Gene Attenuates the Ability of Rabbit Lens Epithelial Cells against H2O2-induced Apoptosis through Down-regulation of the αB-crystallin Gene*
TLDR
The introduction of the human bcl-2 gene into an immortalized rabbit lens epithelial cell line and down-regulation of the αB-crystallin gene reveal that BCL-2 can regulate gene expression in rabbit lenses epithelial cells and reduce resistance to H2O2-induced apoptosis.
Inhibition of proliferation and induction of apoptosis by abrogation of heat-shock protein (HSP) 70 expression in tumor cells
TLDR
Results indicate that H SP70 antisense treatment inhibits the expression of HSP70, which in turn inhibits cell proliferation and induces apoptosis in tumor cells and suggest that HSP 70 is required for tumor cells to proliferate and survive under normal condition.
Sensitization to the Lysosomal Cell Death Pathway upon Immortalization and Transformation
TLDR
It is shown that immortalization and transformation sensitize cells in particular to the cysteine cathepsin-mediated lysosomal death pathway, which may counteract cancer progression and enhance therapeutic responses by sensitizing cells to programmed cell death.
Over‐expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells
TLDR
The results suggest that over‐expression of hsp70 increases the tumorigenic potential of WEHI‐S cells in mice, by allowing these cells to escape from the early TNF‐mediated anti‐tumor immune surveillance.
Cathepsin B Acts as a Dominant Execution Protease in Tumor Cell Apoptosis Induced by Tumor Necrosis Factor
TLDR
Cathepsin B, which is commonly overexpressed in human primary tumors, may have two opposing roles in malignancy, reducing it by its proapoptotic features and enhancingIt by its known facilitation of invasion.
...
1
2
3
4
5
...