AGR2 expression

Exogenous AGR2 combined with AKT agonist IGF- Ⅰ can further enhance the multiplication, migration and invasion of CRC cells. Exogenous AGR2 enhances the multiplication of CRC cells and induces EMT process, the mechanism of which is related to AKT/β-catenin signal pathway.

CAFs drive the growth and metastasis of aggressive PNETs. The CXCR4-SDF1 axis may be a target for antistromal therapy in the treatment of PNET. This study clarifies mechanisms underlying PNET aggressiveness and may guide future therapeutic interventions targeting the tumor microenvironment.

AGR2 is clearly upregulated in the majority of prostate cancer cases, yet a true diagnostic value appears unlikely. In spite of the negative correlation of AGR2 expression with increasing tumour grade, no independent prognostic significance was found in this large-scale study.

These results indicated that acinar cells may act as the origin of human PDAC, and that their presence may be useful for the stratification of human PDAC to predict prognosis.

There was a statistical interaction between AGR2 and FOXA1 on the prognosis of ER-positive breast cancer. The combination of AGR2 and FOXA1 was a more useful marker for the prognosis of ER-positive breast cancer patients.

Low AGR2 expression may predict poorer prognosis. Incorporation of AGR2 improved the specificity of CA125 and HE4 in EOC diagnosis, and may act as a tumor suppressor whose low expression in EOC patients predicted poorer outcomes.

AGR2 gene expression was significantly higher in patients with GBM. Thus, AGR2 gene can be considered as a potential therapeutic target.

Patients with AGR2 low expression could be suitable for combination treatment with immune checkpoint inhibitor agents and TGF-β blockers. Therefore, this study provides a theoretical foundation for developing a strategy for personalized immunotherapy to patients with breast cancer.

Applying this BsAb in a T cell-Tumor cell co-culture system showed that targeting both PD1 and AGR2 with this BsAb induces the attachment of TALL-104 (CD8 T-lymphocytes) cells onto co-cultured H460 AGR2 Lung tumor cells and significantly reduces migration of H460 cells...These effects are significantly reduced with AGR2 expression negative WI38 cells. Our results demonstrate that the AGR2xPD1 BsAb could be a potential therapeutic agent to provide better solid tumor targeting and synergetic efficacy for treating AGR2+ cancer by blocking AGR2 paracrine signaling to reduce tumor survival, and redirecting cytotoxic T-cells into AGR2+ cancer cells.

Mechanically, AFAP1-AS1 sequestered the miR-653-5p and blocked the inhibition of miR-653-5p to AGR2 and stepwise upregulated AGR2 overexpression in LUAD gefitinib resistant cells, resulting gefitinib resistance in LUAD. AFAP1-AS1 promotes gefitinib-resistance LUAD cells through a previously unrecognized miR-653-5p/AGR2 axis, suggesting targeting AFAP1-AS1/miR-653-5p/AGR2 axis might be a promising way for LUAD intervention.

KAI1 and AGR2 may be potential biomarkers for prognosis and metastasis, and they are also promising therapeutic targets for LUAD patients.

No abstract available

AGR2 is highly expressed in UPR-active CSCs and drug-resistant GB cells, and its repression leads to apoptosis, via multiple pathways.

Finally, we performed the GSEA analysis and found that AGR2 was negatively related to IL-17 and NF-kβ signaling pathways. AGR2 was finally determined as the most important prognostic biomarker in BRCA bone metastasis, and it may play a vital role in cancer progression by regulating IL-17 and NF-kB signaling pathways.

In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy.

In this review, we summarize the already known roles and mechanisms of action of the AGR family proteins in digestive diseases, their expression in the healthy digestive tract, and in digestive oncology. At last, we discuss the potential diagnostic and therapeutic implications underlying the biology of AGR proteins.

Induced AGR2 expression was able to rescue the loss of function induced by si-circADAMTS6 in KYSE150 cell. CircADAMTS6 may acts as oncogene by activating AGR2 and the Hippo signaling pathway coactivator YAP in ESCC.

EIF5A2 knockdown inhibited the biological process of cervical cancer cells through modulation of AGR2. The in-depth investigation of the molecular mechanism of EIF5A2 in cervical cancer cells provides new strategies for the prevention and treatment of clinical malignancies.

AGR2 expression was detected in several glioma primary cell lines, both AGR2 and GRp78 were co-localized in tissues and cell lines.It has been linked to drug resistance, a series of cytotoxic studies were conducted to evaluate the link between AGR2 expression and drug resistance founding that AGR2 is significantly expressed in surviving cells.siRNA against AGR2 Exome 2 exhibited the greatest inhibitory impact, demonstrating the significance of its existence.Using double hits results in significant survival inhibition.When siRNA for AGR2 was used in conjunction with Temozolomide or Irinotecan, there was a substantial change in cell density compared to drugs alone,surviving cells are those that express AGR2. Conclusion AGR2 was highly expressed in high-grade GBM and meningioma. It’s one of the CSC markers in the CNS system tumours and part of the UPR machinery.AGR2 expression was shown in the remaining survival cells following drug treatments or using siRNA, indicating AGR2 importance for cell proliferation and survival.Targeting, blocking AGR2 using antibodies and peptides is one way to eliminate cancer in the brain, among other cancer types.

circ_0119412 functioned as an oncogenic driver to promote the malignant development of cervical cancer by targeting the miR-217/AGR2 pathway.

In response to these drugs, particularly doxorubicin, tumor cells can enter into senescence...All these results showed that AGR2 expression in sera and tumors of breast cancer patients is a marker of tumor progression and metastasis occurrence. They also showed that its overexpression regulates CIS escape via activation of the mTOR/AKT signaling pathway.

METTL3 can regulate the expression of MALAT1 through m A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer. METTL3 may modify MALAT1 protein through m A, recruit E2F1 and activate downstream AGR2 expression, thus promoting adriamycin resistance in breast cancer.

The results of this study indicated that LINC01857 was highly expressed in HCC, and it could improve HCC cell proliferation and reduce apoptosis via competitively binding to miR-197-3p, promoting AGR2 and upregulating the AKT and ERK pathways.

ERGI and AGR2 change indicate favorable modulation by acolbifene and appear to provide independent information. Conclusions These results suggest that change in expression of benign breast AGR2 might be a useful addition to change in expression of other classic estrogen response genes in evaluating the potential of novel SERMs such as acolbifene compared to standard SERMs like tamoxifen in early phase prevention trials.

Our study suggests participation of multiple genetic mechanisms, general and specific of each subtype, in the thrombogenesis of AGC patients. If validated, these genetic risk factors, individually or as molecular signatures, could contribute to improve capacity to predict individual thrombotic risk in these patients.

According to the ROC curve, the combined use of studied markers validity was with a sensitivity of 100%, specificity of 96%, PPV 96%, and NPV 100% (p < 0.001; AUC: 0.984). Integrated use of SOX2 and AGR2 biomarkers with serum AGR2 assay holds a promising hope for their future use as predictive markers for early detection of tamoxifen resistance in ER-positive breast cancer patients.

Next, LC-MS/MS was analyzed, and indicating that AGR2vH may be associated with CCA cell proliferation via Wnt/β-catenin signaling pathway activation, which was verified by β-catenin expression and nuclear translocation. The current results provide evidence that AGR2vH upregulation promotes tumorigenicity in CCA cells linked with an alteration of CCA cell proteome.

AGR2 and AGR3 expression were able to differentiate non-BLBC from BLBC. Downregulation of AGR2 and AGR3 was associated with BLBC clinical phenotype. Furthermore, both genes behave different when considering prognosis and molecular stratification.

Finally, overexpression and hypomethylation of AGR2 facilitated the proliferation, invasion and migration of LUAD cells. These results demonstrated that hypomethylation of AGR2 promoter region promoted the expression of AGR2 in LUAD cells, thus promoting the progression of LUAD cells.

AGR2 knockdown enhances therapeutic effects of a COX-2 inhibitor, celecoxib, in CRC metastasis. Collectively, our study reveals a promoting role and molecular mechanisms of iAGR2 in CRC metastasis and uncovers a new tumor microenvironment signal regulating AGR2 expression, which may provide new targets for treating metastatic CRC.

AGR2 expression is correlated with metastasis in Luminal breast cancer.

In addition, AGR2 over-expression caused the re-arrangement of the actin cytoskeletal network. Presumably over-expressed AGR2 up-regulates β-DG post-transcriptionally and facilitates its trafficking, which then causes re-arrangement of the cytoskeletal network, which plays a role in the adhesion and invasion of cancer cells.

Ectopic AGR2 overexpression attenuated the EA-elicited inhibition on the growth of xenograft pancreatic tumor, and negated the EA-induced enhancement of mouse survival. EA ameliorates pancreatic cancer through suppression of AGR2 expression, and future studies in clinical settings are needed to further assess the anti-cancer efficacy of EA.

In conclusion, AGR2 was overexpressed in endometrial cancer and AGR2-induced glucose metabolism facilitated the progression of endometrial carcinoma via the MUC1/HIF-1α pathway. AGR2 may be an effective therapeutic target for endometrial carcinoma.

Moreover, patients with high β-catenin and AGR2 expression showed lower overall survival than those with low expression. In conclusion, our study describes a novel role for AGR2 as a stem cell marker that is highly regulated by canonical Wnt/β-catenin signaling in colorectal cancer.

Meanwhile, we also found the expression of FOXA1 could be inhibited by miR-212-3p, which working as a tumor suppressor downregulated in HCC. We revealed that FOXA1 exerted its biological function by regulating AGR2 expression, and its ectopic expression may be blamed for low expression of miR-212-3p.

Upregulation of C/EBPβ correlated with increased expression and secretion of the interleukin-6 and interleukin-8, inducing angiogenesis and inflammation in Caki-1 cells. In summary, our studies revealed that AGR2 has essential functions in ccRCC progression through upregulation of C/EBPβ and HIF-2α expressions, which affects cell signaling and metabolism.

In conclusion, we revealed for the first time that ZEB1 regulates AGR2 at the transcriptional level, while AGR2 presence contributes to ZEB1 mRNA degradation. Thus, our data identify a new regulatory mechanism between AGR2 and ZEB1, two rivals in the EMT process, tightly associated with the development of metastasis.

Moreover, silencing of LINC01207 and up-regulation of miR-143-5p promoted cell apoptosis and autophagy, corresponding to increased expression of autophagy- and apoptosis-related proteins, in addition to inhibited cell growth. Taken together, silencing of LINC01207 prevents the progression of pancreatic cancer by impairing miR-143-5p-targeted AGR2 inhibition, providing a potential target for pancreatic cancer treatment.

Ectopic AGR2 expression partially negated the H-1-2 inhibitory effect on invasion and migration of pancreatic cells and on xenograft pancreatic tumors growth, and it also compromised the H-1-2 promotional effect on survival of mice. We conclude that H-1-2 suppresses pancreatic cancer by inhibiting hypoxia-induced AGR2 expression, supporting further investigation into its efficacy against pancreatic cancer in clinical settings.