Rab25 associates with a5b1 integrin to promote invasive migration in 3D microenvironments (Develop Cell, 2007, 13:496-510)

報告日期: 2008/12/16
報告時間: 16:00/16:50
報告學生: 蔡宗翰
講評老師: 鄭宏祺
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971216-2.pdf

Rab25 Associates with a5b1 Integrin to Promote Invasive Migration in 3D Microenvironments

 

Caswell P.T. et al., Developmental Cell 2007; 13: 496-510

 

Speaker : 蔡宗翰

Commentator : 鄭宏祺 教授

Time : 2008/12/16 16:10-17:00

Place : Room 602

 

Abstract

 

Rab proteins are members of the Ras superfamily of GTPases that are involved in membrane-trafficking events. Rab25, which is including in Rab11 subfamily and always restricted to an epithelial expression profile. It has been shown to increase the aggressiveness of ovarian and breast tumors both clinically and in mouse models. Integrins are heterodimeric extracellular matrix (ECM) receptors involved in multiple aspects of cell behavior in physiological and pathological contexts. α5β1 integrin is known to influence tumor-cell survival, proliferation, and metastasis, which and its ligand fibronectin (FN) are known to be present in a range of cellular structures such as focal adhesions, focal complexes, fibrillar, and 3D matrix adhesions, which can make stimulatory and inhibitory contributions to cell migration. In this study, the authors found that selective and direct interaction between the β1 integrin cytoplasmic tail and a GTPase of the Rab25. In time-lapse microscopy assay, they found Rab25 promotes an invasive mode of migration on 3D matrices in which it functions to localize and keep α5β1 at the tips of extending pseudopodia.In conclusion, these data demonstrate that Rab25 interacts directly with α5β1 integrin and promotes invasive, metastatic-like migration through FN-rich matrices, and this direct interaction between Rab25 and β1 integrin may in itself be a therapeutic target.

 

References

1. Cheng, K.W. et al., (2004) The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat. Med. 10, 1251–1256.

2. Wang, W. et al., (2004).Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors. Cancer Res. 64, 8585–8594.