Department of General Surgery, Xiantao First People's Hospital Affiliated to Yangtze University, Xiantao, Hubei, China.
Department of General Surgery, Xiantao First People's Hospital Affiliated to Yangtze University, Xiantao, Hubei, China.
Tissue Cell. 2022 Oct;78:101878. doi: 10.1016/j.tice.2022.101878. Epub 2022 Jul 29.
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.
结直肠癌（CRC）是第三大常见癌症，也是癌症相关死亡的第四大主要原因，尽管预后不佳。SIAH E3 泛素蛋白连接酶 2（SIAH2）通过泛素化和蛋白酶体调节多种蛋白质的表达。然而，SIAH2 在结直肠癌肿瘤发生中的生物学作用仍存在争议。在这项工作中，我们发现 SIAH2 是结直肠癌的致癌基因。此外，SIAH2 促进结直肠癌细胞的增殖、迁移、侵袭和集落形成。在机制上，SIAH2 促进了体内和体外的 PI3K/AKT 信号通路。此外，我们发现 PTEN 缺失调节 SIAH2 介导的 PI3K/AKT 信号通路激活。总之，这些发现强调了 SIAH2 在结直肠癌进展中的作用，并为治疗提供了新的见解。
