β2 spectrin-mediated differentiation repressed the properties of liver cancer stem cells through β-catenin.
Yuhua ChenLingling MengHaitao ShangQian DouZhiwen LuLiping LiuZhijun WangXingxing HeYuhu SongPublished in: Cell death & disease (2018)
βII-Spectrin (β2SP), a Smad3/4 adaptor protein during transforming growth factor (TGF) β/Smad signal pathway, plays a critical role in suppressing hepatocarcinogenesis. Dedifferentiation is a distinctive feature of cancer progression. Therefore, we investigated whether the disruption of β2SP contributed to tumorigenesis of hepatocellular carcinoma (HCC) through the dedifferentiation. Down-regulation of β2SP in hepatocytes was observed in cirrhotic liver and HCC. The level of β2SP expression was closely associated with the differentiation status of hepatocytes in rat model of hepatocarcinogenesis and clinical specimens. Transgenic expression of β2SP in HCC cells promoted the differentiation of HCC cells and suppressed the growth of HCC cells in vitro. Efficient transduction of β2SP into liver CSCs resulted in a reduction in colony formation ability, spheroid formation capacity, invasive activity, chemo-resistance properties, tumorigenicity in vivo. In addition, β2 spectrin exerted its effect through β catenin in liver CSCs. In conclusion, β2 spectrin repressed the properties of liver CSCs through inducing differentiation; thus, strategies to restore its levels and activities would be a novel strategy for HCC prevention and differentiation therapy.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- cancer stem cells
- induced apoptosis
- cell cycle arrest
- poor prognosis
- signaling pathway
- oxidative stress
- cell proliferation
- machine learning
- photodynamic therapy
- deep learning
- squamous cell carcinoma
- mesenchymal stem cells
- mass spectrometry
- papillary thyroid
- amino acid
- long non coding rna
- ultrasound guided