Department of Gastrointestinal Surgery 2 Section, Institute of Abdominal Surgery, Key Laboratory of Accurate Diagnosis and Treatment of Cancer, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China.
Cell Death Dis. 2023 Jan 5;14(1):6. doi: 10.1038/s41419-022-05524-y.
Colorectal cancer cannot be completely cured at present, and it is still an important clinical medical problem. TRAF6 is highly expressed in many malignant tumors. However, the role of TRAF6 in colorectal cancer is still controversial, mainly because the specific regulatory mechanism of colorectal cancer is still unclear, and the death mode of colorectal cancer cells has not been elucidated. The recent study found that TRAF6 inhibits necroptosis in colorectal cancer cells via the RIPK1/RIPK3/MLKL signaling pathway. The RIPK1 inhibitor Necrostain-1 inhibits colorectal cancer cell necroptosis via the RIPK1/RIPK3/MLKL signaling pathway. TRAF6 directly interacts with RIPK1 through the polyubiquitination of Lys48-linked RIPK1 and reduces the levels of RIPK1 protein in colorectal cancer cells, leading to necroptosis, thus promoting the proliferation of colorectal cancer cells. The recent study demonstrated that TRAF6 promotes colorectal cell progression by inhibiting the RIPK1/RIPK3/MLKL necroptosis signaling pathway, which may provide a new therapeutic target for colorectal cancer.
目前，结直肠癌无法完全治愈，仍然是一个重要的临床医学问题。TRAF6 在许多恶性肿瘤中高表达。然而，TRAF6 在结直肠癌中的作用仍存在争议，主要是因为结直肠癌的确切调控机制尚不清楚，结直肠癌细胞的死亡方式也尚未阐明。最近的研究发现，TRAF6 通过 RIPK1/RIPK3/MLKL 信号通路抑制结直肠癌细胞的坏死性凋亡。RIPK1 抑制剂 Necrostain-1 通过 RIPK1/RIPK3/MLKL 信号通路抑制结直肠癌细胞的坏死性凋亡。TRAF6 通过多聚泛素化连接的 Lys48 修饰 RIPK1 与 RIPK1 直接相互作用，降低结直肠癌细胞中 RIPK1 蛋白的水平，导致坏死性凋亡，从而促进结直肠癌细胞的增殖。最近的研究表明，TRAF6 通过抑制 RIPK1/RIPK3/MLKL 坏死性凋亡信号通路促进结直肠细胞的进展，这可能为结直肠癌提供新的治疗靶点。
