MYC suppresses cancer metastasis by direct transcriptional silencing of alphav and β3 integrin subunits (Nat Cell Biol, 2012, 14:567-574)

報告日期: 2012/10/12
報告時間: 15:10/16:00
報告學生: 吳嘉恩
講評老師: 鄭宏祺
附件下載: 下載[1229-1348725069-1.pdf] 

MYC suppresses cancer metastasis by direct transcriptional silencing of

av and b3 integrin subunits

Hong Liu, Derek C. Radisky, Dun Yang, Ren Xu, Evette S. Radisky, Mina J. Bissell and J. Michael Bishop

Nature cell biology, 2012, 14(6)

                                     Speaker:Wu, Jia-En                                      Time: 15:1016:00

Commentator: Cheng, Hung-Chi                            Place: Room 602  

Abstract

    MYC, a proto-oncogene, is a transcription factor. It has been proved that overexpression of MYC is strong correlated with tumorigenesis. MYC can transform cells through several different mechanisms, for example changes of cell cycle, differentiation, cell growth, cell migration, apoptosis, genomic stability and angiogenesis1. In some studies, overexpression of MYC is sometimes dissociated from the propensity to metastasis2. Furthermore, overexpression of MYC impair keratinocyte migration3. So, the authors propose that MYC may inhibit the cancer cell motility. In this study, overexpression of MYC increased proliferation of breast cancer cells, but repressed cell migration and invasion in vitro and in vivo. According to the results of tail vein injection in nude mice, they had proved that overexpression of MYC could stimulate cell proliferation and lead to larger tumor, but decrease metastasis in lung and liver. Moreover, cell motility is a dynamic process associated with the binding between cell surface receptors and ligands of extracellular matrix. They found that overexpression of MYC reduced cell attachment to one matrix protein, vitronectin. The avb3 integrin heterodimer is the cell surface receptor for vitronectin. The authors also found that MYC could repress expression of avb3 integrin by direct transcriptional silencing. In addition, ectopic avb3 integrin can recover the migration, invasion and metastasis when MYC overexpression. Finally, in the MYC-depleting study, the authors found that b3 integrin can induce cell invasion and MYC can prevent its function. This study point out that av and b3 integrin are crucial element in the metastasis and MYC can inhibit these protein to prevent cancer metastasis. This is important to the strategy to target MYC in cancer therapy.

Reference

1.Meyer N, Penn LZ. Reflecting on 25 years with MYC (2008) Nat Rev Cancer, 8 (12).

2.Boxer RB et al. Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. (2004) Cancer Cell, 6(6)

3.Frye M et al. Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interactions with the local microenvironment. (2003) Development, 130(12)