AMIGO2 (Adhesion Molecule With Ig Like Domain 2)

Protein profiling from the Human Protein Atlas further confirmed elevated AMIGO2 expression in tumors. Together, these findings demonstrate that AMIGO2 promotes PAAD aggressiveness by enhancing adhesion- and EMT-associated pathways, establishing it as a potential prognostic biomarker and therapeutic target in pancreatic cancer.

Moreover, combining AMIGO2 targeting with anti-PD-1 therapy yielded superior efficacy. Consistent validation was also obtained in a clinical cohort of HNSCC and premalignancy patients.

AMIGO2 expression was positively correlated with expression of existing cancer stem cell markers in multiple organ cancer cell lines. These results demonstrate that AMIGO2 accelerates the malignant progression of human cancer cells by inducing a cancer stem cell-like phenotype.

PAAD patients with high AMIGO2 expression were more sensitive to BRD4 inhibitor BI-2536. The growth of PAAD cells was found to be inhibited upon knockdown of AMIGO2. AMIGO2 was identified as prognostic factor in PAAD, suggesting its potential as a biomarker and therapeutic target for PAAD patients.

Our work provides a framework for integrating DRS and DEG omics data. Our results suggest a role for dysregulation of m6A modifications in pathways implicated in ET resistance in BC.

However, the co-expression of AMIGO2 and Ki-67 was identified as an independent prognostic factor for OS. In conclusion, AMIGO2 expression may be considered a novel biomarker for the identification of the risk of recurrence and reduced survival in patients with bladder cancer, and could be used as a rationale for initiating treatment, such as radiation therapy, chemotherapy or immunotherapy, after radical cystectomy.

This study used multi-omics analysis combined with machine learning to construct a novel NEPC classifier and classification system. NEP100 provides a clinically actionable framework for NEPC diagnosis and subtyping.

AMIGO2-containing sEVs derived from GC cells actively modify the hepatic microenvironment by activating HSCs and inducing IL-8 secretion, which promotes GC cell migration into the liver parenchyma. This process contributes to the formation of a pre-metastatic niche, highlighting AMIGO2-containing sEVs as potential therapeutic targets for preventing liver metastasis.

Next, we used clinically available signal inhibitors (MEK inhibitor trametinib, JAK inhibitor ruxolitinib, and JNK inhibitor SP600125), and found that ruxolitinib inhibits AMIGO2 expression more stably. Using the MKN45 gastric cancer cells, we confirmed that ruxolitinib could prevent liver metastasis of human cancer cells. These results demonstrate that pharmacological inhibition of AMIGO2 expression in tumor cells is a promising novel strategy to prevent and control liver metastasis.

© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Activation of the TGFβ/Smad signaling pathway was found involved in AMIGO2-induced EMT, and treatment with the TGFβ receptor inhibitor LY2109761 suppressed AMIGO2-induced EMT...These results suggest that the nuclear translocation of AMIGO2 induces EMT to promote CRC invasion by activating the TGFβ/Smad signaling pathway. Thus, AMIGO2 is an attractive therapeutic target for inhibiting EMT and metastatic CRC progression.