Inhibition of autophagy may suppress the development of hepatoblastoma.

Abstract

Hepatoblastoma (HB) is a rare cancer but represents the most common liver malignancy in children under 3 years of age. Nevertheless, a clear understanding of the pathogenesis is lacking. Although the treatment of HB has been dramatically improved by combining chemotherapy regimens with surgery, its fatal outcome of fast development and recurrence makes new treatment strategies for HB, based on an improved understanding of the pathogenesis, essential. Autophagy is believed to be important in the progression of cancers. However, the role of autophagy in HB remains to be elucidated. Here, we show that autophagy is activated in HB tissues and cells under the conditions of starvation or chemotherapy, coupled with the over-expression of autophagic-related genes BECN1 and ATG5. Suppression of autophagy with pharmacological agents and small interfering RNAs significantly increased cell apoptosis and retarded proliferation in response to nutrition deprivation and treatment with chemotherapeutics. Our data demonstrate that the BECN1 and ATG5-dependent phosphoinositide 3-kinase (PI3K) signaling pathway is essential for the survival of HB cells and their tolerance to chemotherapy and starvation-induced death, and suggests that modifying such autophagic genes may suppress the development of HB, thus offering a therapeutic potential for patients with HB.

• Authors: Yanxin Chang, Lei Chen, Yuan Liu, Liang Hu, Liang Li, Qianqian Tu, Ruoyu Wang, Mengchao Wu, Jiahe Yang, Hongyang Wang
• Journal: The FEBS journal (FEBS J) Vol. 278 Issue 24 Pg. 4811-23 (Dec 2011) ISSN: 1742-4658 [Electronic] England
• PMID: 21972944 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors Journal compilation © 2011 FEBS.

Chemical References

• ATG5 protein, human
• Apoptosis Regulatory Proteins
• Autophagy-Related Protein 5
• BECN1 protein, human
• Beclin-1
• Membrane Proteins
• Microtubule-Associated Proteins
• RNA, Small Interfering
• Phosphatidylinositol 3-Kinases

Topics

• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (biosynthesis, physiology)
• Autophagy (drug effects, physiology)
• Autophagy-Related Protein 5
• Beclin-1
• Cell Line, Tumor
• Child, Preschool
• Hepatoblastoma (drug therapy, etiology)
• Humans
• Liver Neoplasms (drug therapy, etiology)
• Membrane Proteins (biosynthesis, physiology)
• Microtubule-Associated Proteins (biosynthesis, physiology)
• Phosphatidylinositol 3-Kinases (physiology)
• RNA, Small Interfering (pharmacology)
• Signal Transduction (physiology)