NOTCH3 expression

In extending those dependencies, we demonstrate that MUC1-C is necessary for NOTCH3 expression, self-renewal capacity and tumorigenicity. The findings that MUC1 associates with ∆Np63, SOX2 and NOTCH3 expression by scRNA-seq analysis further indicate that MUC1-C drives the HNSCC stem cell state and is a target for suppressing HNSCC progression.

Additionally, NFATc1 directly binds to the sex determining region Y-box 2 (SOX2) promoter and modifies stemness in GC. In conclusion, our work illustrated that FPR3 played a negative role in GC progression by modulating NFATc1-mediated glycolysis and stemness in a calcium-dependent manner, providing potential insights into cancer therapy.

Further, NDMM patients with high NOTCH3 expression exhibited worse responses to Bortezomib (BOR)-based therapies...Moreover, genetic or pharmacologic inhibition of CXCL12 in NOTCH3OE MM cells restored sensitivity to BOR regimes in vitro and in human bones bearing NOTCH3OE MM tumors cultured ex vivo. Our clinical and preclinical data unravel a novel NOTCH3-CXCL12 pro-survival signaling axis in the TME and suggest that osteocytes transmit chemoresistance signals to MM cells.

Therefore, WWTR1-AS1 may upregulate Notch3 through miR-136 to increase cancer cell stemness in CSCC.

Interference with the interaction between MR-1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells, which is a previously overlooked treatment option in NSCLC. In summary, interference with the interaction between MR-1 and NICD3 in the progression of lung cancer may be a promising therapeutic target.

Bulk RNA-sequencing data demonstrated that NOTCH3 expression correlated with poor survival in stroma-rich patients and that a T cell-inflamed gene signature only predicted survival in patients with low NOTCH3. Collectively, this study provides valuable insights into the role of NOTCH3 in regulating tumor stroma biology, warranting further studies to elucidate the clinical implications of targeting NOTCH3 signaling.

These cells exhibited reduced expression of the base-excision repair proteins PARP1 and APE1, along with increased sensitivity to ara-c and cisplatin. These data point to a pathway in which Notch-3 signaling can regulate DNA repair within colon tumor cells and suggests that targeting Notch-3 may be an effective approach to rendering colon tumors sensitive to chemotherapeutic drugs.

Clinically, high expression of NOTCH3, miR-223 or low expression of ZEB1 were related to good prognosis of breast cancer patients. The current study reports a novel NOTCH3/miR-223/ZEB1 axis, which can inhibit the proliferation and invasion of breast cancer cells, and may serve as a potential biomarker for the prognosis of breast cancer.

The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

Therefore, NOTCH3 may be employed as a prognostic biomarker in PCa patients. NOTCH3 could be a therapeutic target for PCa patients, particularly those who have developed docetaxel resistance.

In this study, we successfully established a prognostic anoikis-connected signature using machine learning. This model may aid in evaluating patient prognosis, clinical characteristics, and immune treatment modalities for melanoma.

NOTCH pathway genes appear to play an important role in the progression of OC by regulating immune cells, endocrine resistance, Th1 and Th2 cell differentiation, and oxidative phosphorylation. JAG2 and NOTCH1 are potential biomarkers and therapeutic targets for the treatment of OC.

Nevertheless, the JAG1/JAG2/DLL1/DLL4 transcriptome was diminished in anti-TNF good responders with myeloid pathotype and was unaltered in the fibroid pathotype except for DLL4. Taken together, our findings suggest that RA myeloid Notch ligands can serve as markers for anti-TNF responsiveness and trans-activate Notch receptors expressed on RA FLS and/or endothelial cells.

We report that cyclooxygenase 1 and 2 differentially regulate undifferentiated spermatogonia/spermatogonial stem cell differentiation. Cyclooxygenases regulate Notch3 expression, with the Notch pathway targeted by PGD2. These data suggest an interaction between the eicosanoid and Notch signaling pathways that may be critical for the development of spermatogonial stem cells and subsequent spermatogenesis, cautioning about using cyclooxygenase inhibitors in infants.

P=N/A, N=100, Recruiting, Columbia University | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: May 2023 --> May 2024

Conclusion Complete clinical data, a comprehensive pathohistological report, estimation of HIF1 alpha, VEGFR1, NOTCH3 expression and number of CD34 positive micro-vessels on a 2mm biopsy incorporated in tissue microarray could select pT1 patients that require intensive follow-up and a trimodal approach to treatment. Understanding the role of molecular pathways in chemio/radiotherapy response could bring new possibilities for better controlling and personalized, molecular treatment of bladder cancer.

Genetic or pharmacological perturbation of NOTCH3 conferred chemosensitivity of NPC in vitro and overexpression of NOTCH3 enhanced chemoresistance of NPC in vivo. Together, these data indicated that genome-wide enhancer reprogramming activates NOTCH3 to confer chemoresistance of NPC, suggesting that targeting NOTCH3 may provide a potential therapeutic strategy to effectively treat advanced chemoresistant NPC.

Our molecular docking analysis suggested that gamma mangostin (gMG), a xanthone, formed complexes with INFG/STAT1/NOTCH3 better than celecoxib. Finally, we utilized a DOX-resistant TNBC tumoroid-bearing mouse model to demonstrate that gMG treatment significantly delayed tumor growth, reduced CAF generation, and improved DOX sensitivity. Further investigations are warranted for clinical translation.

Our data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 may serve as a potential biomarker and therapeutic target for TNBC.

Our study demonstrates that EZH2, Notch3, and Nanog are important prognostic factors. Enhancer of zeste homologue 2 could maintain the self-renewal of OS cells, where the Notch3 pathway activation may be involved.

We also found that mice whose tumors had high levels of Notch3 had a greater density of immunosuppressive macrophages in the TME, which was associated with elevated levels of TNF-α. Overall, our data suggest that patients with EGFR-mutant NSCLC whose tumors harbor high levels of Notch3 may have worse clinical outcomes and response to immune checkpoint inhibitors due to Notch3 promoting an immunosuppressive TME.

In summary, depletion of HOTAIR functionally decreased OCSC phenotypes and malignant potential and reprogrammed HGSOC to a less stem-like phenotype. There is an urgent need to develop new therapeutic strategies to target OCSCs and overcome chemoresistant OC, and the results of this study suggest that targeting HOTAIR in combination with epigenetic therapies may represent a novel therapeutic strategy to prevent tumor relapse in OC.

Notch3-null tumors were enriched in Mybl2 mRNA signature and protein expression. Hence, our study reinforces the anti-tumoral role of Notch3 in breast tumorigenesis.

The interaction of Notch3 receptor and DLL4 ligand accelerates oncogenesis, progression, and poor prognosis of breast cancer patients. Notch3 protein may serve as one of biomarker to independently predict prognosis of patients.

Colosphere forming ability was also reduced in cells with inhibited Smad3. These results indicate a key role of TGF-β signaling in Notch1-induced tumorigenesis, and suggest a potential use for Smad3 inhibitors in combination with Notch1 inhibitors that are already in use for CRC treatments.

Our study illustrated that Notch3 could facilitate the progression of CRC by increasing the infiltration of macrophages and MDSCs to promote the immunosuppressive tumor microenvironment. Targeting Notch3 specifically is a potentially effective treatment for CRC.

Gender, local recurrence, tumor resection, postoperative radio-chemotherapy, WHO grade, recurrence, and ATRX expression were all associated with NOTCH3 expression. ASAP3 was shown to be positively associated with NOTCH3 (r = 0.337, P = 0.000). Therefore, ASAP3 and NOTCH3 as oncogene factors have the potential to be prognostic biomarkers and therapeutic targets in adult glioma.

The expression of Jagged 1, Notch 3, Snail, and Hes 1 were also increased again in HCT116 cells treated with Xiaotansanjiefang medication plus with Jagged 1 Fc chimera protein. The presented study may provide a promising strategy to treat and prevent colorectal cancer.

The therapeutic benefit of TKF against liver fibrosis results from inhibition of YAP and Notch3-Hes1 pathways, indicating that TKF may be a novel therapeutic candidate for liver fibrosis.

Finally, high expression of NOTCH3 is associated with prolonged survival in patients with luminal breast cancer. These results highlight an unexpected tumor-suppressive function for Notch3 in the parous mammary gland through restriction of PI-MEC expansion.

In summary, our preliminary results suggested that Notch3 might inhibit EMT by trans-activating GSK3β in breast cancer cells. The suppression of Notch3 expression may contribute to EMT by transcriptionally downregulating GSK3β in breast cancer.

These data showed that DLL1 might play a pivotal role in the prognosis of DLBCL through immune system modulation and interaction with cancer-related pathways. This suggests that DLL1 could be a novel prognostic biomarker, risk stratification factor, and attractive therapeutic target for DLBCL.

These data showed that DLL1 might play a pivotal role in the prognosis of DLBCL through immune system modulation and interaction with cancer-related pathways. This suggests that DLL1 could be a novel prognostic biomarker, risk stratifi cation factor, and attractive therapeutic target for DLBCL.

P=N/A, N=100, Recruiting, Columbia University

NIH3T3 and OVCAR3 co-cultured SNFT cells showed maximum proliferation, invasion, and cisplatin resistance among all the heterotypic/homotypic cellular partners...Additionally, metastatic HGSOC tumors had higher VEGFA than corresponding primary tumors. This study thus demonstrates the tumoral and non-tumoral cell-mediated differential Notch3 activation imparting its tumorigenic effects through two critical molecular regulators, VEGFA and p21, during EOC progression.

Further evaluation confirmed that LMP2A induces ETV5 transcription, but repress GATA6 and NOTCH3 expression. ETV5, GATA6 and NOTCH3 are the candidate targets of LMP2A in gastric cancer.