Multi-faceted role of HSP40 in cancer

Mitra, Aparna; Shevde, Lalita A.; Samant, Rajeev S.

doi:10.1007/s10585-009-9255-x

Cited by 85 publications

(78 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, most of the HSP40 family proteins have been reported to be inversely correlated with high-grade malignancy, and HSP40 family proteins have been reported to function as tumor suppressors (40). In this study, we found that DNAJB8 was expressed in several kinds of cancer cells, including RCCs, and that it was preferentially expressed in the CSC/CIC population.…”

Section: Discussionmentioning

confidence: 56%

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

et al. 2012

View full text Add to dashboard Cite

Cancer stem-like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB8 overexpression increased the percentage of side population (SP) cells representing CSCs in RCC cells, enhancing their tumor-initiating ability. Conversely, attenuation of DNAJB8 decreased SP cells and reduced tumor-initiating ability. The utility of DNAJB8 as an immunologic target was established in DNA vaccination experiments. Compared with immunization with the tumor-associated antigen survivin, which was expressed in both CSCs and non-CSCs in RCC, immunization with Dnajb8 expression plasmids yielded stronger antitumor effects. Together, our findings suggest that DNAJB8 plays a role in CSC maintenance and that it offers a candidate for CSC-targeting immunotherapy in RCC.

show abstract

Section: Discussionmentioning

confidence: 56%

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Tid1 isoforms were also found to be involved in extra-mitochondrial protein interactions and functions (see below). These functions include regulation of cell death, proliferation, and signal transduction (Mitra et al 2009;Syken et al 1999). It was shown that the two isoforms differ in their non-mitochondrial functions due to differences in their abilities to interact with cytosolic and nuclear proteins (Lu et al 2006).…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Reactivation of protein aggregates by mortalin and Tid1—the human mitochondrial Hsp70 chaperone system

Iosefson

Sharon

Goloubinoff

et al. 2012

Cell Stress and Chaperones

View full text Add to dashboard Cite

The mitochondrial 70-kDa heat shock protein (mtHsp70), also known in humans as mortalin, is a central component of the mitochondrial protein import motor and plays a key role in the folding of matrix-localized mitochondrial proteins. MtHsp70 is assisted by a member of the 40-kDa heat shock protein co-chaperone family named Tid1 and a nucleotide exchange factor. Whereas, yeast mtHsp70 has been extensively studied in the context of protein import in the mitochondria, and the bacterial 70-kDa heat shock protein was recently shown to act as an ATP-fuelled unfolding enzyme capable of detoxifying stably misfolded polypeptides into harmless natively refolded proteins, little is known about the molecular functions of the human mortalin in protein homeostasis. Here, we developed novel and efficient purification protocols for mortalin and the two spliced versions of Tid1, Tid1-S, and Tid1-L and showed that mortalin can mediate the in vitro ATP-dependent reactivation of stable-preformed heat-denatured model aggregates, with the assistance of Mge1 and either Tid1-L or Tid1-S co-chaperones or yeast Mdj1. Thus, in addition of being a central component of the protein import machinery, human mortalin together with Tid1, may serve as a protein disaggregating machine which, for lack of Hsp100/ClpB disaggregating co-chaperones, may carry alone the scavenging of toxic protein aggregates in stressed, diseased, or aging human mitochondria.

show abstract

“…Furthermore, three stress-inducible molecular chaperones involved in protein folding, DNAJB1, DNAJB4, and DNAJB9, were increased by nifurtimox plus TM treatment. As molecular chaperones, these proteins bind to unfolded proteins or mutant proteins to ensure proper protein folding (74,75). Since oxidative stress causes the accumulation of damaged proteins, the upregulation of these genes signifies a cytoprotective response to the proteotoxic stress induced by the nifurtimox plus TM treatment.…”

Section: Discussionmentioning

confidence: 99%

Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma

Koto

Lescault²,

Brard³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Medulloblastoma, a neuroectodermal tumor arising in the cerebellum, is the most common brain tumor found in children. We recently showed that nifurtimox induces production of reactive oxygen species (ROS) and subsequent apoptosis in neuroblastoma cells both in vitro and in vivo. Tetrathiomolybdate (TM) has been shown to decrease cell proliferation by inhibition of superoxide dismutase-1 (SOD1). Since both nifurtimox and TM increase ROS levels in cells, we investigated whether the combination of nifurtimox and TM would act synergistically in medulloblastoma cell lines (D283, DAOY). Genome-wide transcriptional analysis, by hybridizing RNA isolated from nifurtimox and TM alone or in combination treated and control cells (D283) on Affymetrix exon array gene chips was carried out to further confirm synergy. We show that nifurtimox and TM alone and in combination decreased cell viability and increased ROS levels synergistically. Examination of cell morphology following drug treatment (nifurtimox + TM) and detection of caspase-3 activation via Western blotting indicated that cell death was primarily due to apoptosis. Microarray data from cells treated with nifurtimox and TM validated the induction of oxidative stress, as many Nrf2 target genes (HMOX1, GCLM, SLC7A11 and SRXN1) (p<10 -5 ) were upregulated. Other genes related to apoptosis, oxidative stress, DNA damage, protein folding and nucleosome formation were differentially involved in cells following treatment with nifurtimox + TM. Taken together, our results suggest nifurtimox and TM act synergistically in medulloblastoma cells in vitro, and that this combination warrants further studies as a new treatment for medulloblastoma.

show abstract

Multi-faceted role of HSP40 in cancer

Cited by 85 publications

References 92 publications

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

Reactivation of protein aggregates by mortalin and Tid1—the human mitochondrial Hsp70 chaperone system

Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma

Contact Info

Product

Resources

About