AMIGO2 enhances the invasive potential of colorectal cancer by inducing EMT.

Autor: Izutsu R; Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan., Osaki M; Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan. osamitsu@tottori-u.ac.jp.; Chromosomal Engineering Research Center, Tottori University, Yonago, Tottori, Japan. osamitsu@tottori-u.ac.jp., Seong H; Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan., Ogata S; Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan., Sato R; Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan., Hamada JI; Advanced Research Promotion Center, Health Sciences University of Hokkaido, Ishikari-Tobetsu, 061-0293, Japan.; School of Nursing and Social Services, Health Sciences University of Hokkaido, Ishikari-Tobetsu, 061-0293, Japan., Okada F; Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.; Chromosomal Engineering Research Center, Tottori University, Yonago, Tottori, Japan.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2024 Oct 08. Date of Electronic Publication: 2024 Oct 08.
DOI: 10.1038/s41417-024-00842-z
Abstrakt: 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.)
Databáze: MEDLINE
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