Cleavage of Endoplasmic Reticulum Proteins in Hepatocellular Carcinoma: Detection of Generated Fragments in Patient Sera

Chignard, Nicolas; Shang, Sufen; Wang, Hong; Marrero, Jorge A.; Bréchot, Christian; Hanash, Samir M.; Beretta, Laura

doi:10.1053/j.gastro.2006.02.058

Cited by 72 publications

(69 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may only reflect a saturation of the KDEL receptor ER retrieval system but could also be functionally significant. This is well illustrated by calreticulin, which is found in the serum of cancer patients as revealed by the presence of autoantibodies (11) and protein fragments (6). In addition, proteolytic fragments specific of BiP and PDI have also been identified in the serum of HCC patients (6).…”

Section: Modulation Of Er-associated Functions In Cancermentioning

confidence: 87%

“…Similar to what has already been reported for the expression of ER-resident proteins, various posttranslational modifications occur under specific environmental conditions targeting the ER but have also been found constitutively present in cancers. For instance, various KDEL-containing proteins, such as GRP78/BiP, GRP94, or PDI (and related proteins), have been found to be secreted in cancer cells (6). This may only reflect a saturation of the KDEL receptor ER retrieval system but could also be functionally significant.…”

Section: Modulation Of Er-associated Functions In Cancermentioning

confidence: 99%

See 1 more Smart Citation

Integrated Endoplasmic Reticulum Stress Responses in Cancer

et al. 2007

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) has emerged as a major site of cellular homeostasis regulation, particularly in the unfolded protein response, which is being found to play a major role in cancer and many other diseases. Here, we address ER-mediated signaling and regulations in the context of environmental challenges in cancer, such as hypoxia, angiogenesis, and chemotherapeutic resistance, and we discuss how ER-resident molecular machines become deregulated and involved in cancer-related pathology. Further exploration of how the ER senses, signals, and adapts to stress may redefine and deepen our understanding of its functions in cancer pathobiology. [Cancer Res 2007;67(22):10631-4]

show abstract

Section: Modulation Of Er-associated Functions In Cancermentioning

confidence: 87%

Section: Modulation Of Er-associated Functions In Cancermentioning

confidence: 99%

Integrated Endoplasmic Reticulum Stress Responses in Cancer

et al. 2007

View full text Add to dashboard Cite

show abstract

“…HCV also upregulates cellular FLIP (to inhibit caspase-8; ref. 36), and stimulates the generation of CRT fragments that become detectable in the serum of infected patients (37) and that might act as competitive antagonists of CRT receptors on DCs. These findings point to the possibility, that viruses might have developed specific strategies to subvert the CRT exposure pathway and hence to avoid the immune recognition of dying virus-infected cells.…”

Section: Clinical-translational Advancesmentioning

confidence: 99%

Immunogenic Tumor Cell Death for Optimal Anticancer Therapy: The Calreticulin Exposure Pathway

Zitvogel

Kepp

Senovilla

et al. 2010

Clinical Cancer Research

345

275

View full text Add to dashboard Cite

In response to some chemotherapeutic agents such as anthracyclines and oxaliplatin, cancer cells undergo immunogenic apoptosis, meaning that their corpses are engulfed by dendritic cells and that tumor cell antigens are presented to tumor-specific CD8 + T cells, which then control residual tumor cells.One of the peculiarities of immunogenic apoptosis is the early cell surface exposure of calreticulin (CRT), a protein that usually resides in the lumen of the endoplasmic reticulum (ER). When elicited by anthracyclines or oxaliplatin, the CRT exposure pathway is activated by pre-apoptotic ER stress and the phosphorylation of the eukaryotic translation initiation factor eIF2α by the kinase PERK, followed by caspase-8-mediated proteolysis of the ER-sessile protein BAP31, activation of the pro-apoptotic proteins Bax and Bak, anterograde transport of CRT from the ER to the Golgi apparatus and exocytosis of CRT-containing vesicles, finally resulting in CRT translocation onto the plasma membrane surface. Interruption of this complex pathway abolishes CRT exposure, annihilates the immunogenicity of apoptosis, and reduces the immune response elicited by anticancer chemotherapies. We speculate that human cancers that are incapable of activating the CRT exposure pathway are refractory to the immunemediated component of anticancer therapies.

show abstract

“…The expression of an iron-storage protein, tissue ferritin light chain, was identified as severely reduced, whereas the corresponding transcript was not changed (Park et al, 2002b). Our group has applied proteomic tools to the comparative analysis of protein profiles between HCC and adjacent non-tumor liver tissues as a means of discovering novel molecular markers (Chignard et al, 2006). Forty-seven protein spots that showed reproducible variation were identified by MS, corresponding to proteins encoded by 23 distinct genes.…”

Section: Tumor Tissuesmentioning

confidence: 99%