Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu

Abstract

Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream pathways, or microenvironment signals. Cancer cells may exploit this aberrant signaling to “educate” the surrounding microenvironment cells toward a pro-tumoral behavior. This may occur because of key cytokines secreted by tumor cells or it may involve the microenvironment through the activation of Notch signaling in stromal cells, an event mediated by a direct cell-to-cell contact and resulting in the increased secretion of several pro-tumorigenic cytokines. Up to now, review articles were mainly focused on Notch contribution in a specific tumor context or immune cell populations. Here, we provide a comprehensive overview on the outcomes of Notch-mediated pathological interactions in different tumor settings and on the molecular and cellular mediators involved in this process. We describe how Notch dysregulation in cancer may alter the cytokine network and its outcomes on tumor progression and antitumor immune response.

Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway

“…Tumor cells can excrete many types of cytokines, such as VEGFA and TNF-α, thereby altering the permeability of microvascular networks and causing transudative and exudative ascites 43 , 44 . Macrophage and inflammatory cells could induce pyroptosis or necroptosis, release several necrotic materials and inflammatory mediators, and increase the volume of ascites 8 , 45 .…”

Mutations in the notch signalling pathway are associated with enhanced anti‐tumour immunity in colorectal cancer

“…25 In this study, we first analysed the GSE10 8989 data set to investigate the effects of Notch signalling pathway mutations on the immunophenotype of CRC, which differs from the aim It has been reported that the dysregulation of the Notch pathway in the tumour skews the local cytokine milieu, shaping the immunological landscape and affecting tumour growth, progression and metastases. 26 The Notch signalling pathway is a key regulator of inflammatory-related cytokines in cancers, such as IL-10, 27 TGFβ, 28 IL-6, 29 CCL2 30 and CXCL12. 31 In our study, we observed that the expression of CXCR3 was up-regulated in cluster 4 (mainly from tumours of patients with Notch pathway mutations) compared with cluster 0 (mainly from tumours of non-mutation patients) of CD8 + T cells.…”

Endostar Rebuilding Vascular Homeostasis and Enhancing Chemotherapy Efficacy in Cervical Cancer Treatment

“…Notch signaling is an evolutionarily rmly conserved signaling system.It widely exists in all known animal cells and regulates the proliferation, differentiation and apoptosis of tissues and cells.VEGF-notch signal cause tumor abnormal vascular growth through controlling tip and stalk cells balance [18,19].…”