Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway.

ABSTRACT:

Background

Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown.

Methods

We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistochemical analyses with tissue microarray were performed.

Results

Knockdown or loss of Smad4 induced tumorigenicity, migration, invasion, angiogenesis, metastasis, and 5-FU resistance. Smad4 expression in mouse tumours regulated cell-cycle regulatory proteins leading to Rb phosphorylati

SUBMITTER: Zhang B 

PROVIDER: S-EPMC3929873 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature