Notch signaling, hypoxia, and cancer

Guo, Mingzhou; Niu, Yang; Xie, Min; Liu, Xiansheng; Li, Xiaochen

doi:10.3389/fonc.2023.1078768

Cited by 16 publications

(7 citation statements)

References 258 publications

(193 reference statements)

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“…Epithelial-mesenchymal transition (EMT) is the initial process of tumor cells taken to invade and metastasize 41 . Under hypoxia, multiple signaling pathways were activated, including TGF-β, NF-κB, phosphoinositide 3-kinase (PI3K)/Akt, and Notch-1 42,43 . As a highly conserved pathway, the notch signaling pathway plays a critical role in the initiation and progression of different cancers 44 .…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced DTL promotes the proliferation, metastasis, and sorafenib resistance of Hepatocellular Carcinoma through Notch Signaling Pathway

Gao,

Chen,

et al. 2024

Preprint

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Denticleless E3 ubiquitin protein ligase homolog (DTL), the substrate receptor of the CRL4A complex, plays a central role in genome stability. Even though the oncogenic function of DTL has been investigated in several cancers, its specific role in Hepatocellular Carcinoma (HCC) still needs further elucidation. Data from a clinical cohort (n = 209), RNA-sequencing, and public database (TCGA and GEO) were analyzed, indicating that DTL is closely related to patient prognosis and could serve as a promising prognostic indicator in HCC. Functionally, DTL promoted the proliferation, metastasis, and sorafenib resistance of HCC in vitro. In the orthotopic tumor transplantation and tail vein injection model, DTL promoted the growth and metastasis of HCC in vivo. Mechanically, we revealed for the first time that DTL was transcriptionally activated by hypoxia-inducible factor 1α (HIF-1α) under hypoxia and functioned as a downstream effector molecule of HIF-1α. DTL facilitates HCC cell proliferation, metastasis, and epithelial-mesenchymal transition through the Notch pathway. These results suggested that DTL may be a potential biomarker and therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-induced DTL promotes the proliferation, metastasis, and sorafenib resistance of Hepatocellular Carcinoma through Notch Signaling Pathway

Gao,

Chen,

et al. 2024

Preprint

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“…The Hes-1 gene is one of the downstream genes necessary for the activation and function of the Notch/Jagged signal pathway [36]. The Notch/Jagged signal pathway is involved in different physiological and disease processes [37,38]. Importantly, Jagged-1 is closely involved in hematopoietic function [39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway

Wang,

Bi,

Zhang

et al. 2023

Stem Cells International

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Background. Poor graft function (PGF) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT). Current therapies, such as CD34+ cell infusion, have shown limited effectiveness. Conversely, mesenchymal stem cells (MSCs) show potential in addressing PGF. Adipose-derived mesenchymal stem cells (ADSCs) effectively support long-term hematopoietic stem cell proliferation. Therefore, this study aimed to investigate the mechanisms underlying the long-term hematopoietic support provided by ADSCs. Methods. ADSCs were isolated from mice and subsequently identified. In vitro experiments involved coculturing ADSCs as feeders with Lin-Sca-1+c-kit+ (LSK) cells from mice for 2 and 5 weeks. The number of LSK cells was quantified after coculture. Scanning electron microscopy was utilized to observe the interaction between ADSCs and LSK cells. Hes-1 expression was assessed using western blot and real-time quantitative PCR. An γ-secretase inhibitor (GSI) was used to confirm the involvement of the Jagged-1/Notch-1/Hes-1 pathway in LSK cell expansion. Additionally, Jagged-1 was knocked down in ADSCs to demonstrate its significance in ADSC-mediated hematopoietic support. In vivo experiments were conducted to study the hematopoietic support provided by ADSCs through the infusion of LSK, LSK + fibroblasts, and LSK + ADSCs, respectively. Mouse survival, platelet count, leukocyte count, and hemoglobin levels were monitored. Results. ADSCs showed high-Jagged-1 expression and promoted LSK cell proliferation. There was a direct interaction between ADSCs and LSK cells. After coculture, Hes-1 expression increased in LSK cells. Moreover, GSI-reduced LSK cell proliferation and Hes-1 expression. Knockdown of Jagged-1 attenuated ADSCs-mediated promotion of LSK cell proliferation. Furthermore, ADSCs facilitated hematopoietic recovery and promoted the survival of NOD/SCID mice. Conclusion. The hematopoietic support provided by ADSCs both in vivo and in vitro may be mediated, at least in part, through the Jagged-1/Notch-1 signaling pathway. These findings provide valuable insights into the mechanisms underlying ADSCs-mediated hematopoietic support and may have implications for improving the treatment of PGF following HSCT.

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“…[44] Studies have shown that Notch signaling pathway plays a critical role in the development and progression of tumors. [45] Over-expressed Notch-1 receptor can up-regulate the expression level of cell division cycle 20 (Cdc-20) protein in OS cells, so as to improve the viability of OS cells. [46] Additionally, over-expressed Notch-3 receptor can affect the invasion and metastasis of OS by regulating the expression levels of downstream target genes Hes1 and matrix metalloenzyme 7 (MMP-7), so as to evaluate the prognosis of OS patients.…”

Section: Os-associated Signaling Pathwaymentioning

confidence: 99%

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Liu,

Jiang,

et al. 2024

Medicine

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Osteosarcoma (OS) has a high recurrence rate, disability rate, mortality and metastasis, it brings great economic burden and psychological pressure to patients, and then seriously affects the quality of life of patients. At present, the treatment methods of OS mainly include radiotherapy, chemotherapy, surgical therapy and neoadjuvant chemotherapy combined with limb salvage surgery. These treatment methods can relieve the clinical symptoms of patients to a certain extent, and also effectively reduce the disability rate, mortality and recurrence rate of OS patients. However, because metastasis of tumor cells leads to new complications, and OS cells become resistant with prolonged drug intervention, which reduces the sensitivity of OS cells to drugs, these treatments still have some limitations. More and more studies have shown that traditional Chinese medicine (TCM) has the characteristics of “multiple targets and multiple pathways,” and can play an important role in the development of OS through several key signaling pathways, including PI3K/AKT, Wnt/β-catenin, tyrosine kinase/transcription factor 3 (JAK/STAT3), Notch, transforming growth factor-β (TGF-β)/Smad, nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor E2-related factor 2 (Nrf2), Hippo/YAP, OPG/RANK/RANKL, Hedgehog and so on. In this paper, the signaling pathways of cross-interference between active ingredients of TCM and OS were reviewed, and the development status of novel OS treatment was analyzed. The active ingredients in TCM can provide therapeutic benefits to patients by targeting the activity of signaling pathways. In addition, potential strategies for targeted therapy of OS by using ferroptosis were discussed. We hope to provide a unique insight for the in-depth research and clinical application of TCM in the fields of OS growth, metastasis and chemotherapy resistance by understanding the signaling crosstalk between active ingredients in TCM and OS.

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Notch signaling, hypoxia, and cancer

Cited by 16 publications

References 258 publications

Hypoxia-induced DTL promotes the proliferation, metastasis, and sorafenib resistance of Hepatocellular Carcinoma through Notch Signaling Pathway

Hypoxia-induced DTL promotes the proliferation, metastasis, and sorafenib resistance of Hepatocellular Carcinoma through Notch Signaling Pathway

Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

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