Mechanisms of anterior gradient-2 regulation and function in cancer

Brychtová, Veronika; Mohtar, M. Aiman; Vojtěšek, Bořivoj; Hupp, Ted R.

doi:10.1016/j.semcancer.2015.04.005

Cited by 46 publications

(47 citation statements)

References 89 publications

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“…AGR2 is a protein disulfide isomerase (PDI) localized to the endoplasmic reticulum (ER) [8]. Expression of AGR2 is found in many solid tumor types including prostate, pancreatic, breast, lung, gastrointestinal and oral [9]. More significantly, cancer cells secrete AGR2 and the protein is found on the cell surface [10-12], whereas normal AGR2 + cells do not have expression on the cell surface as the protein is not secreted and is localized to the cell interior [13].…”

Section: Introductionmentioning

confidence: 99%

“…AGR2 could activate ER stress response genes [11], to stimulate cell proliferation of AGR2-negative pancreatic tumor cells, and to enhance drug resistance [10]. Cell surface AGR2 could alter signaling pathways by modulating other cell surface proteins through its disulfide isomerization activity [9]. Other functional aspects for AGR2 reported in the literature include regulation of amphiregulin expression [20], promotion of cell adhesion [21], cancer spread via regulation of cathepsins [11], and cancer cell survival [10].…”

Section: Introductionmentioning

confidence: 99%

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Cancer-secreted AGR2 induces programmed cell death in normal cells

et al. 2016

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Anterior Gradient 2 (AGR2) is a protein expressed in many solid tumor types including prostate, pancreatic, breast and lung. AGR2 functions as a protein disulfide isomerase in the endoplasmic reticulum. However, AGR2 is secreted by cancer cells that overexpress this molecule. Secretion of AGR2 was also found in salamander limb regeneration. Due to its ubiquity, tumor secretion of AGR2 must serve an important role in cancer, yet its molecular function is largely unknown. This study examined the effect of cancer-secreted AGR2 on normal cells. Prostate stromal cells were cultured, and tissue digestion media containing AGR2 prepared from prostate primary cancer 10-076 CP and adenocarcinoma LuCaP 70CR xenograft were added. The control were tissue digestion media containing no AGR2 prepared from benign prostate 10-076 NP and small cell carcinoma LuCaP 145.1 xenograft. In the presence of tumor-secreted AGR2, the stromal cells were found to undergo programmed cell death (PCD) characterized by formation of cellular blebs, cell shrinkage, and DNA fragmentation as seen when the stromal cells were UV irradiated or treated by a pro-apoptotic drug. PCD could be prevented with the addition of the monoclonal AGR2-neutralizing antibody P3A5. DNA microarray analysis of LuCaP 70CR media-treated vs. LuCaP 145.1 media-treated cells showed downregulation of the gene SAT1 as a major change in cells exposed to AGR2. RT-PCR analysis confirmed the array result. SAT1 encodes spermidine/spermine N1-acetyltransferase, which maintains intracellular polyamine levels. Abnormal polyamine metabolism as a result of altered SAT1 activity has an adverse effect on cells through the induction of PCD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cancer-secreted AGR2 induces programmed cell death in normal cells

et al. 2016

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“…The molecular mechanisms underlying these wide-ranging biological pathways trigged by AGR2 are still not completely defined and as the AGR2 gene is confined to vertebrates, the AGR2 gene pathway cannot be dissected using powerful genetic systems like yeast, flies, or worms [18]. However, emerging functions in the AGR2 pathway focus on (i) identifying its client proteins as it mediates protein folding in the endoplasmic reticulum [19] and as it stimulates receptor maturation [20] [21]; (ii) understanding its function in the endoplasmic reticulum in response to unfolded protein responses [22], (iii) defining the nature of its monomer-dimer equilibrium in tis chaperone cycle [23]; and (iv) understanding the significance of its highly specific peptide docking function which is relatively unique for a molecular chaperone [24] [25].…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry analysis of the oxidation states of the pro-oncogenic protein anterior gradient-2 reveals covalent dimerization via an intermolecular disulphide bond

Clarke¹,

Murray

Faktor

et al. 2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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“…AGR2, anterior gradient 2, is a member of protein disulfide isomerase (PDI) family resides in the endoplasmic reticulum (ER) (32). AGR2 expression has been found in prostate: primary and metastatic, pancreatic, breast, lung, gastrointestinal and oral solid tumors (33,34). In PvsN analysis, overexprission of this gene has been observed and also had pretty high degree and betweenness centralities.…”

Section: Igfbp-3 Expression Level Following Reduction Of Foxa1 Signifmentioning

confidence: 99%

Identification of potential biomarkers associated with pathogenesis of primary prostate cancer based on meta-analysis approaches

Sepahi

Piran

et al. 2020

Preprint

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Worldwide prostate cancer (PCa) is recognized as the second most common diagnosed cancer and the fifth leading cause of cancer death among men globally. Rising incidence rates of PCa have been observed over the last few decades. It is necessary to improve prostate cancer detection, diagnosis, treatment and survival .However, there are few reliable biomarkers for early prostate cancer diagnosis and prognosis. In the current study, systems biology method was applied for transcriptomic data analysis to identify potential biomarkers for primary PCa.We firstly identified differentially expressed genes (DEGs) between primary PCa and normal samples. Then the DEGs were mapped in Wikipathways and gene ontology database to conduct functional categories enrichment analysis. 1575 unique DEGs with adjusted p-value < 0.05 were achieved from two sets of DEGs. 132 common DEGs between two sets of DEGs were retrieved. The final DEGs were selected from 60 common upregulated and 72 common downregulated genes between datasets. In conclusion, we demonstrated some potential biomarkers (FOXA1, AGR2, EPCAM, CLDN3, ERBB3, GDF15, FHL1, NPY, DPP4, and GADD45A) and HIST2H2BE as a candidate one which are tightly correlated with the pathogenesis of PCa.

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Mechanisms of anterior gradient-2 regulation and function in cancer

Cited by 46 publications

References 89 publications

Cancer-secreted AGR2 induces programmed cell death in normal cells

Cancer-secreted AGR2 induces programmed cell death in normal cells

Mass spectrometry analysis of the oxidation states of the pro-oncogenic protein anterior gradient-2 reveals covalent dimerization via an intermolecular disulphide bond

Identification of potential biomarkers associated with pathogenesis of primary prostate cancer based on meta-analysis approaches

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