E2A suppresses invasion and migration by targeting YAP in colorectal cancer cells.

Abstract

BACKGROUND:

E2A gene, which encodes two basic helix-loop-helix (bHLH) transcription factors E12 and E47, has been identified as regulator of B lymphoid hematopoiesis and suppressor of lymphoma. E47 protein was found to decrease E-cadherin expression and induce epithelial-mesenchymal transition (EMT). However, the role of E2A in colorectal cancer (CRC) metastasis is still elusive.

METHODS:

qRT-PCR and semi-qRT-PCR were performed to determine mRNA level of E2A in CRC specimens and colorectal cancer cells. RNAi was employed to downregulate E2A expression and subsequent protein level change was evaluated by immunoblot. Cell invasion and migration capacity were detected by transwell assay using cell culture inserts with or without basement membrane matrix, respectively.

RESULTS:

E2A expression was decreased in metastatic CRC tissues. Invasion and migration assays showed downregulation of E2A increased metastatic capacity of CRC cells while forced expression of E12 or E47 could offset this effect. Both E12 and E47 suppressed EMT induced by E2A downregulation. Moreover, Yes-Associated Protein (YAP) was a downstream target of E2A and suppression of YAP inhibited the pro-migration/invasion of E2A deficiency.

CONCLUSION:

Our results suggest that E2A suppresses CRC cell metastasis, at least partially if not all, by inhibiting YAP expression.

• Authors: Hongchao Zhao, Ao Huang, Pu Li, Yingjun Quan, Bo Feng, Xuehua Chen, Zhihai Mao, Zhenggang Zhu, Minhua Zheng
• Journal: Journal of translational medicine (J Transl Med) Vol. 11 Pg. 317 (Dec 26 2013) ISSN: 1479-5876 [Electronic] England
• PMID: 24369055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Basic Helix-Loop-Helix Transcription Factors
• DNA Primers
• Phosphoproteins
• TCF3 protein, human
• Transcription Factors
• YAP-Signaling Proteins
• YAP1 protein, human

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Base Sequence
• Basic Helix-Loop-Helix Transcription Factors (physiology)
• Colorectal Neoplasms (metabolism, pathology)
• DNA Primers
• Epithelial-Mesenchymal Transition
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Phosphoproteins (metabolism)
• Real-Time Polymerase Chain Reaction
• Transcription Factors
• YAP-Signaling Proteins