Invasion and metastasis of a mammary tumor involves TGF-beta signaling - PubMed (original) (raw)

. 2001 Jan 1;91(1):76-82.

doi: 10.1002/1097-0215(20010101)91:1<76::aid-ijc1012>3.0.co;2-8.

J J Kobie, V Mack, R S Wu, L Meade-Tollin, C L Arteaga, N Dumont, D Besselsen, E Seftor, M J Hendrix, E Katsanis, E T Akporiaye

Affiliations

Invasion and metastasis of a mammary tumor involves TGF-beta signaling

J A McEarchern et al. Int J Cancer. 2001.

Abstract

Several studies have correlated escape from TGF-beta-mediated cell cycle arrest with the tumorigenic phenotype. Most often, this escape from growth control has been linked to dysfunctional TGF-beta receptors or defects in the TGF-beta-mediated SMAD signaling pathway. In this report, we found that highly metastatic 4T1 mammary carcinoma cells express functional TGF-beta receptors capable of initiating SMAD-mediated transcription, yet are not growth inhibited by TGF-beta1. We further observed that TGF-beta directly contributes to the metastatic behavior of this cell line. Exposure to TGF-beta caused 4T1 cells to undergo morphological changes associated with the metastatic phenotype and invade more readily through collagen coated matrices. Furthermore, expression of a dominant negative truncated type II receptor diminished TGF-beta signaling and significantly restricted the ability of 4T1 cells to establish distant metastases. Our results suggest that regardless of 4T1 resistance to TGF-beta-mediated growth inhibition, TGF-beta signaling is required for tumor invasion and metastases formation.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources