Cytochrome B5 type A alleviates HCC metastasis via regulating STOML2 related autophagy and promoting sensitivity to ruxolitinib

Cell Death Dis. 2022 Jul 18;13(7):623. doi: 10.1038/s41419-022-05053-8.

Abstract

The incidence of hepatocellular carcinoma (HCC) is increasing in the world. However, its role and underlying molecular mechanism in HCC progression remain unclear. We found that CYB5A plays a key role in HCC metastasis by inhibiting the JAK1/STAT3 pathway through binding to STOML2. CYB5A combined with STOML2 can predict the outcome of patients. To demonstrate the effect of CYB5A on JAK1 inhibitor function, we applied Ruxolitinib in metastatic tumors with high CYB5A expression and found that it slowed disease progression and prolonged survival in mice. To the best of our knowledge, this study is the first to report the Ruxolitinib effect on the metastatic ability of HCC cells in vivo and in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Blood Proteins / metabolism*
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cytochromes b5 / pharmacology
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • Neoplasm Metastasis
  • Nitriles
  • Pyrazoles
  • Pyrimidines

Substances

  • Blood Proteins
  • Membrane Proteins
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • STOML2 protein, human
  • ruxolitinib
  • Cytochromes b5