2. Academic Validation
  3. TRAF6 regulates the abundance of RIPK1 and inhibits the RIPK1/RIPK3/MLKL necroptosis signaling pathway and affects the progression of colorectal cancer

TRAF6 regulates the abundance of RIPK1 and inhibits the RIPK1/RIPK3/MLKL necroptosis signaling pathway and affects the progression of colorectal cancer

  • Cell Death Dis. 2023 Jan 5;14(1):6. doi: 10.1038/s41419-022-05524-y.
Penghang Lin # 1,  Chunlin Lin # 1,  Ruofan He 1 2,  Hui Chen 1 2,  Zuhong Teng 1 2,  Hengxin Yao 1 2,  Songyi Liu 1 2,  Robert M Hoffman 3 4,  Jianxin Ye 5,  Guangwei Zhu 6
Affiliations

Affiliations

  • 1 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.
  • 2 Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China.
  • 3 AntiCancer, Inc., San Diego, CA, USA.
  • 4 Department of Surgery, University of California, San Diego, CA, USA.
  • 5 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. yejianxinfuyi@126.com.
  • 6 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. zgwzsy@126.com.
  • # Contributed equally.
PMID: 36604411 DOI: 10.1038/s41419-022-05524-y
Abstract

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.

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