Our data provide an explanation to Jag1 dependence in cancer, and reveal that Jag1-Notch1 interference provides therapeutic benefit in a subset of colorectal cancer and FAP syndrome patients.
A statistically significant positive association between the expression levels of FAM83H-AS1 and those of Notch1 or Hes1 in CRC tissues was analyzed by Spearman's correlation analysis.
However, the expression of Notch‑1 and Jagged1 was comparable in colorectal carcinoma and colorectal adenoma tissues, and in paracancerous and normal colorectal tissues.
In conclusion, our study substantiates the role of AKT and Notch1 in cell proliferation, angiogenesis, and EMT of CRC cells and demonstrates that VJ may be a viable therapeutic option to counter AKT-induced cell proliferation and tumor outgrowth in CRC.
Overall, our findings illuminated a novel STRAP-NOTCH1-HES1 molecular axis as a CSC regulator in colorectal cancer, with potential implications to improve treatment of this disease.<i></i>.
Lower positive expression rate of RUNX3 and higher positive expression rate of Notch1 and Jagged 1 were observed in CRC tissues than those in normal adjacent tissues with a negative correlation, and the expression levels were associated with the differentiation degree, TNM staging, lymph node metastasis and tumor invasion depth (all P<0.05).
These findings suggest that patients with metastatic CRC that harbor a gain in NOTCH1 gene copy number have worse survival and that targeting this patient population with a Notch1 antibody may yield improved outcomes.
Taken together, our data indicate a new role of miR-139-5p/NOTCH-1 pathway in the drug resistance of CRC cells to 5-FU, which may be a promising therapeutic target for the anti-MDR treatment of CRC.
Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged.
Our findings support an important role of p27 in Notch1-dependent oncogenic signaling and suggest that Notch1 is a promising target for an experimental therapy of colorectal carcinoma.
Both of these tumors exhibited elevated baseline levels of Notch pathway activation as well as an increase in NOTCH1 gene copy number when compared with the two CRC explants (CRC026 and CRC027) where tumors reappeared quickly after termination of treatment.