Download Role of tumor suppressor WOX1 in breast cancer cell migration

Role of tumor suppressor WOX1 in breast cancer cell migration
WOX1 在乳癌轉移中扮演的角色
Student: Pei-Yi Chou
Advisor: Dr. Nan-Shan Chang
Abstract
Background: WW domain-containing oxidoreductase, also known as WWOX/WOX1,
acts as a proapoptotic protein and tumor suppressor. Loss of heterozygosity and
chromosomal rearrangement of the WOX1 gene is associated with ovarian, breast,
hepatocellular, and prostate carcinomas. In addition, loss of WOX1 expression results
in tumorigenesis. WOX1 is also associated with malignancy of cancers. Decreased or
absence of WOX1 protein family is observed in metastatic breast cancer cells. It is
known that WOX1 physically binds p53 and induces apoptosis. Mutant-p53 promotes
TGF-induced metastasis by forming mutant-p53/Smad complex. In addition,
TGF-mediated TIAF1 (TGF1-induced antiapoptoic factor 1) self-aggregation is
prevented by the binding of Smad4. These studies indicate that WOX1 may regulate
cell migration through coordination with molecules such as p53 and TIAF1.
Objective: To investigate whether WOX1 suppresses breast cancer cells,
MDA-MB-231 cell and MCF-7 cell migration via the coordination with p53 and
TIAF1.
Result: Overexpression of WOX1 in both MDA-MB-231 and MCF-7 cells led to
decrease of cell migration significantly. Knockdown of WOX1 and dominant negative
WOX1 increased cell migration. Moreover, cotransfection with WOX1 and TIAF1 or
p53 decreased MDA-MB-231 cell migration synergistically as proved by wound
healing assay. Adherence-independent growth of MDA-MB-231 cells was suppressed
by coexpression of WOX1and TIAF1 as determined by soft agarose assay.
Conclusion: WOX1 suppresses MDA-MB-231 and MCF-7 breast cancer cell
migration. Together, WOX1 and p53 or TIAF1 block cancer cell migration,
suggesting cell migration is regulated by the coordination of WOX1, p53, and TIAF1.