Evidence for a role of p53, WWOX and TIAF1 as tumor suppression axis
Abstract
Tumor suppressor WWOX or WOX1 is frequently lost in many malignant tumors. Here we demonstrated that Wwox exon 1‐ deletion mouse embryonic fibroblasts (MEF Wwox−/−) migrated individually and faster than wild type Wwox+/+ cells. Normally, the wild type cells aligned together tightly and migrated collectively. WOX1 physically interacts with p53 and TIAF1 (TGF‐beta1‐induced antiapoptotic factor). Transiently overexpressed WOX1 suppressed the migration of breast MDAMB‐ 231 and MCF‐7 cells. Knockdown of WOX1 by small interfering RNA, or ectopic expression with dominant‐negative WOX1, increased the migration. While TIAF1 is an effector of the TGF‐beta/Smad signaling, TGF‐beta1 promoted Wwox+/+ MEF cell migration, but had had no significant effect on knockout MEF cell migration. Interestingly, TGF‐ beta2 increased wild type cell migration and suppressed knockout cell migration. Coexpression of WOX1, TIAF1, and/or p53 suppressed cancer cell migration and adherence‐independent growth. Together, WOX1 plays a regulatory role in TGF‐beta‐mediated cell migration. WOX1/p53/TIAF1 is a potential axis of tumor suppression. (Supported by DoD, USA, and NSC and NHRI, Taiwan)
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2012
- Source ID
- 10.1096/fasebj.26.1_supplement.782.3
Entities
People
- Li-jin Hsu
- Ming-hui Lee
- Nan-Shan Chang
- Pei-yi Chou
- Sing-ru Lin
- Yee- Hsin Lin
Organizations
- National Cheng Kung University
- National Science and Technology Council
- United States Department of Defense