These data explained the underlying mechanism of Smad4 contribution on VEGF-C expression during metastasis where ASLNC07322 functions vitally as a switch in colon cancer.
The present study focused on the effect of <i>miR-144</i> and SMAD4 on colon cancer in order to find the novel gene therapy target for the treatment of colon cancer.
However, the role of SMAD-4 gene in other cancers has not been completely explained, therefore in the present study we tried to find the role of this gene in colon cancer.
SMAD4 mutation was associated with colon cancer more so than with rectal cancer (odds ratio 2.85; p<0.001), female sex (odds ratio 1.71; p = 0.02), and shorter overall survival than in wild-type SMAD4 cases (median, 29 months versus 56 months; hazard ratio 2.08; p<0.001 [log-rank test]).
We investigated endogenous Smad4 expression in 7 human colorectal cancer cell lines, and found that six of colon cancer cell lines existed with loss of Smad4.
Here, we describe the establishment and use of colon cancer cell line model systems to dissect the functional roles of TGFβ and Smad4 inactivation in the manifestation of a malignant phenotype.
We evaluated the role of TGF-beta/Smad signaling on cell proliferation, migration, invasion, tumorigenicity, and metastasis in Smad4-null colon carcinoma cell lines (MC38 and SW620) and in those that transgenically express Smad4.
Using cell viability assays, the effect of these compounds was validated on four colon cancer cell lines: HCT-116 and HCT-15 (SMAD4-expressing), and HT-29 and COLO-205 (SMAD4-negative).
Recent studies show the presence of BMP receptor 1a mutations in juvenile polyposis and frequent Smad4 mutations in colon cancer, suggesting that aberrations in BMP signaling play an important role in intestinal cancer pathogenesis.
The TGF-beta-resistant human colon cancer cell line HT-29 has inactivated TbetaRII and deficient expression of RUNX3 and Smad4, which are involved in the TGF-beta signaling pathway.
The data suggested that restoration of Smad4 in Smad4-deficient cells may provide a potential therapeutic strategy for intervention of colon cancer migration and metastasis.
Here, we utilized the SMAD4-null SW480 colon cancer cell line to examine BMPs effect on a potential target gene, PTEN, and how its expression might be regulated.
Analysis of development of colon cancer in (adult) elf+/-/Smad4+/-, elf+/-, Smad4+/-, and gut epithelial cells from elf-/- mutant mouse embryos pinpoints the defect to hyperplasia/adenoma transition.
Loss of SMAD4 expression may play a more prominent role in colon cancer than anticipated based on genetic evidence, but not in mutator phenotype tumours.