SIAH2 regulates colorectal cancer tumorigenesis via PI3K/ATK signaling pathway. (October 2022)

• Record Type: Journal Article
• Authors: Hu, Yongbo; He, Yiming; Liu, Wei; Yu, Shun; Wei, Yabing; Bai, Shaohua; Su, Yu; Xiao, Bin
• Is Part Of: Tissue & cell. Volume 78(2022)
• Publication Date: 2022-10
• Subjects: SIAH2 -- AKT -- PTEN -- Colorectal cancer; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2022.101878
• Languages: English
• ISSNs: 0040-8166

Abstract

Abstract: Colorectal cancer (CRC) is the third most common cancer and the 4th leading cause of cancer-related deaths, although with a dismal prognosis. The SIAH E3 Ubiquitin Protein Ligase 2 ( SIAH2 ) regulates the expression of multiple proteins via ubiquitination and proteasome. However, the biological role of SIAH2 in colorectal cancer tumorigenesis remains controversial. In this work, we found that SIAH2 is an oncogene in colorectal cancer. Moreover, SIAH2 promoted colorectal cancer cell proliferation, migration, invasion, and colony formation. Mechanistically, SIAH2 promoted the PI3K / AKT signaling pathway both in vivo and in vitro . Besides, we discovered that PTEN loss regulates SIAH2 -mediated PI3K / AKT signaling pathway activation. In summary, these findings highlight the role of SIAH2 in colorectal cancer progression and provide novel insights for treatment. Highlights: In our study, we innovatively demonstrated that SIAH2 acted as an oncogene in colorectal cancer. We confirmed that SIAH2 positively regulated PI3K/AKT signaling pathway in vivo and vitro via destabilizing PTEN. These findings might provide a novel sight for colorectal cancer treatment.