TERT promoter mutations (13.1% of R/M cases) were mutually exclusive with both NOTCH1 mutations (q = 3.3 × 10-4) and MYB/MYBL1 fusions (q = 5.6 × 10-3), suggesting discrete, alternative mechanisms of tumorigenesis.
We specifically discovered that some factor in the embryonic microenvironment could suppress Notch1 pathway in the cancer cells, leading to a reduction in tumorigenesis and invasiveness.
SNORD89 deteriorates the prognosis of ovarian cancer patients by regulating Notch1-c-Myc pathway to promote cell stemness and acts as an oncogene in ovarian tumorigenesis.
This study reports a Notch-1 dependent enrichment of CSC properties during dysplastic progression and a Notch-1 independent dysplastic cell-fibroblast interaction during oral carcinogenesis.
However, 4-NQO-induced tumorigenesis assays revealed that tumor onset occurred earlier in N1cKO mice than in wild-type littermates, and the tumors arose preferentially from the Notch1-negative epithelium, indicating the tumor susceptibility of Notch1-deficient epithelium.
One of the underlying challenges is that two of the four known human Notch paralogs, NOTCH1 and 2, share very high structural similarity but play opposing roles in some tumorigenesis pathways.
Then the enhanced notch1, notch2, Jagged1, Jagged2, DLL1 and DLL4 expression were detected in RCC CSCs and blockage of Notch1 or notch2 using pharmacological inhibitor MRK-003 or its endogenous inhibitor Numb resulted in loss of its stemness features: self-renewal, chemoresistance, invasive and migratory potential, and tumorigenesis in vivo.
These findings demonstrated that Notch 1 was associated with CCRCC carcinogenesis and progression, the underlying mechanism of which was that Notch 1 acted as an activator for cell proliferation and a suppressor for cell apoptosis through the Akt/mTOR signaling-dependent pathway in CCRCC.
Taken together, these results suggest that Notch1 pathway and miR-151-5p interplay with p53 in a reciprocal regulation loop in controlling gastric carcinogenesis.
Notch1 may be a potential therapeutic regimen towards renal cell carcinoma, and JNK/p38 may serve as an important molecular mechanism for Notch1-mediated carcinogenesis.