在我们之前的研究中，我们确定了两性蛋白诱导基因和开放阅读框2（AMIGO2）作为肝转移的驱动基因，并发现癌细胞中AMIGO2的表达会恶化结直肠癌（CRC）患者的预后。上皮间质转化（EMT）是结直肠癌获得恶性表型的触发因素，例如侵袭潜力，导致转移。然而，AMIGO2 表达在 CRC 细胞侵袭能力中的作用仍不清楚。因此，本研究旨在检测 AMIGO2 表达并阐明其诱导 EMT 和促进 CRC 侵袭的机制。研究发现 TGFβ/Smad 信号通路的激活参与 AMIGO2 诱导的 EMT，并且使用 TGFβ 受体抑制剂 LY2109761 治疗可抑制 AMIGO2 诱导的 EMT。使用 CRC 样本的研究表明，AMIGO2 表达在侵袭前沿高度上调，其中 AMIGO2 表达定位于细胞核，并与 EMT 标志物表达相关。这些结果表明AMIGO2的核转位通过激活TGFβ/Smad信号通路诱导EMT促进CRC侵袭。因此，AMIGO2 是抑制 EMT 和转移性 CRC 进展的有吸引力的治疗靶点。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

In our previous studies, we identified amphoterin-inducible gene and open reading frame 2 (AMIGO2) as a driver gene for liver metastasis and found that AMIGO2 expression in cancer cells worsens the prognosis of patients with colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) is a trigger for CRC to acquire a malignant phenotype, such as invasive potential, leading to metastasis. However, the role of AMIGO2 expression in the invasive potential of CRC cells remains unclear. Thus, this study aimed to examine AMIGO2 expression and elucidate the mechanisms by which it induces EMT and promotes CRC invasion. 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. Studies using CRC samples showed that AMIGO2 expression was highly upregulated in the invasive front, where AMIGO2 expression was localized to the nucleus and associated with EMT marker expression. 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.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.