|
  
- 积分
- 785
- 威望
- 785
- 包包
- 1506
|
Nat Cell Biol. 2009 Nov;11(11):1287-96. Epub 2009 Oct 18.
% q+ d) C8 A9 Y) CLocalized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility.8 s1 m' N8 j! f8 }
7 T+ z n2 t; k% E3 q; r& ]" {Giampieri S, Manning C, Hooper S, Jones L, Hill CS, Sahai E.- G: |% b8 T* s- G2 K
! C: v, ?, d" L2 y9 ~5 v
Tumour Cell Biology Laboratory, CR-UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
! n3 @2 c$ W1 y+ m* Z" P% T; r k. r% h. t4 f1 e2 _) Y4 y
Comment in:
$ a# Q5 b, K ]2 P+ P9 z9 {9 v' y3 l9 a
* Nat Cell Biol. 2009 Nov;11(11):1281-4. - m0 h m* Q( ~( ]5 \
L7 \& h$ ~ Y$ s
Abstract
, F$ s3 k% ?: V) Z# B/ {* q- [0 h3 Q( J0 u+ \' K9 S2 Z- U
Here we use intravital imaging to demonstrate a reversible transition to a motile state as breast cancer cells spread. Imaging primary tumours revealed heterogeneity in cell morphology and motility. Two distinct modes of motility were observed: collective and single-celled. By monitoring the localization of Smad2 and the activity of a TGFbeta-dependent reporter gene during breast cancer cell dissemination, we demonstrate that TGFbeta signalling is transiently and locally activated in motile single cells. TGFbeta1 switches cells from cohesive to single cell motility through a transcriptional program involving Smad4, EGFR, Nedd9, M-RIP, FARP and RhoC. Blockade of TGFbeta signalling prevented cells moving singly in vivo but did not inhibit cells moving collectively. Cells restricted to collective invasion were capable of lymphatic invasion but not blood-borne metastasis. Constitutive TGFbeta signalling promoted single cell motility and intravasation but reduced subsequent growth in the lungs. Thus, transient TGFbeta signalling is essential for blood-borne metastasis. |
附件: 你需要登录才可以下载或查看附件。没有帐号？注册
-
总评分: 威望 + 10
包包 + 10
查看全部评分
|
发表于 2010-4-9 09:58
发表于 2010-4-9 10:16
