Researchers Discover A Key Factor Governing Lung Cancer Cell Plasticity

Tumor metastasis is the leading cause of high lethality for human cancer patients. Scientists have discovered that the epithelial-mesenchymal plasticity plays critical roles in achieving the long-distance metastasis of cells. Recently, researchers from Chinese Academy of Sciences (CAS) uncovered that hepatocyte nuclear factor 6 (HNF6) is a key transcription factor governing human lung cancer cell plasticity.

Epithelial plasticity is important for the reversible biological process called epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET), through which cell’s identity can be changed. EMT and MET have increasingly been recognized to be implicated in the metastatic cascade of tumors, a process researchers have only began to understand in recent years.

YUAN Xinwang and his colleagues, guided by Dr. SONG Jianguo at Shanghai Institute of Biochemistry and Cell Biology, CAS, detected a rapid and sustained decrease of the HNF6 expression during TGF-β induced EMT. And HNF6 was positively correlated with the epithelial characteristics and negatively correlated with the mesenchymal properties in lung cancers. Besides, cells with HNF6 depletion underwent spontaneously EMT and became highly motile in the lung cancer, whereas overexpression of HNF6 significantly inhibited the migration and invasive growth of lung cancer cells by the induction of MET.

Further study demonstrated that HNF6 regulated p53, a well-known tumor suppressor that also involved in the regulation of epithelial plasticity, through directly transcriptional activation of its promoter. Examination of HNF6 expression in human lung cancer tissues also revealed that HNF6 was positively correlated with both the epithelial marker E-cadherin and tumor suppressor p53. These data provide a new insight into the molecular mechanism of EMT and MET during lung cancer progression, which may help to further explore the regulation of lung cancer cell plasticity and effective control of lung cancer cell migration and metastasis.

This study entitled “Hepatocyte Nuclear Factor 6 suppresses the migration and invasive growth of lung cancer cells through p53 and the inhibition of epithelial-mesenchymal transition” was published in The Journal of Biological Chemistry on Sep 10^th, 2013. The work was supported by the grants from Chinese Ministry of Science and Technology and Natural Science Foundation of China.

CONTACT:
SONG Jianguo
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai, China
Tel: 86-21-54921167
Email: jgsong@sibcb.ac.cn