The Notch signaling pathway is a critical component of vascular formation and morphogenesis in both development and disease. Compelling evidence indicates that Notch signaling is required for the induction of arterial‑cell fate during development and for the selection of endothelial tip and...

The Notch pathway is essential for maintaining neural progenitor cells (NPCs) in the developing brain. Activation of the pathway is sufficient to maintain NPCs, whereas loss‑of‑function mutations in the critical components of the pathway cause precocious neuronal differentiation and NPC...

Proper embryonic development and normal tissue homeostasis require a series of molecular processes, regulating cell growth, differentiation and apoptosis. Perturbation in any of these processes invariably contributes to the development of cancer. In particular, defects in apoptosis are seen in...

The Notch pathway powerfully influences stem cell maintenance, development and cell fate and is increasingly recognized for the key roles it plays in cancer. Notch promotes cell survival, angiogenesis and treatment resistance in numerous cancers, making it a promising target for cancer...

Notch 1 to 4 and the p53 clan, comprising p53, p63 and p73 plus numerous isoforms thereof, are gene transcription regulators that are critically involved in various aspects of cell differentiation, stem cell maintenance and tumour suppression. It is thus perhaps no surprise that extensive...

Notch signaling is an important regulator of skeletogenesis at multiple developmental stages. The Notch signaling pathway is involved in the promotion of somite segmentation, patterning and differentiation into sclerotome pre-chondrogenic cells to allow for appropriate axial skeleton...

In recent years, a substantial body of evidence has accumulated to support the notion that signaling pathways known to be important during embryonic development play important roles in regulating self‑renewing tissues and tumorigenesis. In this context, Notch signaling is now recognized as...

Notch function in the hair follicle has been mainly studied by use of transgenic mice carrying either loss or gain of function mutations in various members of the pathway. These studies revealed that whereas embryonic development of the hair follicle can be achieved without Notch, its...

The innermost (basal) layer of the skin epidermis consists of proliferative progenitors which give rise to multiple differentiating layers providing a barrier that keeps the inside of the body moist and protects the body from outside assaults by physical, environmental and biological factors....

Cancer metastasis is the leading cause of cancer‑related deaths all over the world at present. Accumulated researches have demonstrated that cancer metastasis is composed of a series of successive incidents, mainly including epithelial‑mesenchymal transition (EMT), malignant cell...

Notch signaling exerts multiple important functions in the hematopoietic system. Notch1‑mediated signals are essential to induce the onset of definitive hematopoiesis within specialized domains of hemogenic endothelium in the fetal dorsal aorta. In contrast, Notch is dispensable for the...

Notch is a membrane bound transcription factor and it plays fundamental roles in many cell‑cell interaction events usually involving directly neighboring cells relating an extrinsic signal of a sending cell to the nucleus of the receiving cell to modulate gene expression patterns in this...

Increasing evidence indicates that Notch signaling contributes to physiologic processes, including development, differentiation and tumorigenesis, either as a tumor promoter or suppressor depending on the cellular context, level of expression and cross‑talk with other signaling systems....

Notch signaling plays an essential role in development and homeostasis of multiple organs including the lung. Dysregulation of Notch signaling has been implicated in various lung diseases including lung cancer. Here we review functions of Notch signaling in coordinating events during lung...

The kidney is the body’s filter, responsible for the removal of metabolic waste and the excretion or reabsorption of electrolytes to control blood composition and pH balance. The functional unit of this filter is the nephron, whose segmented architecture has been largely conserved in form...

In humans and other species, Notch‑signaling is of critical importance for carcinogenesis in several organs, including the skin. Interestingly, Notch‑signaling appears to exert opposite roles in skin carcinogenesis as compared to carcinogenesis in other tissues. While the Notch1 receptor...

Regulated intramembrane proteolysis (RIP) is a highly conserved signaling paradigm whereby membrane‑bound signaling proteins are cleaved in their transmembrane region and then released into the cytoplasm to act as signaling molecules. In most if not all cases intramembrane cleavage is...

Subpopulations of cancer cells with stem cell‑like characteristics, termed cancer stem cells, have been identified in a wide range of human cancers. Cancer stem cells are defined by their ability to self‑renew as well as recapitulate the original heterogeneity of cancer cells in culture...

It has been more than two decades since Notch has been identified as an oncogene in mouse mammary tumor virus‑infected mice. Since this discovery, activated Notch signaling and up‑regulation of tumor‑promoting Notch target genes have been observed in human breast cancer. In addition,...

Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which...

Sensory hair cells (HCs) and their associated nonsensory supporting cells (SCs) exhibit a typical mosaic pattern in each of the sensory patches in the inner ear. Notch signaling has been considered to conduct the formation of this mosaic pattern through one of its famous functions, known as...

Notch is a single‑pass transmembrane receptor that mediates the local cell‑cell interactions necessary for many cell‑fate decisions. The extra cellular domain of Notch contains a tandem array of epidermal growth factor‑like (EGF‑like) repeats. Some of these EGF‑like repeats are...

The Notch signaling pathway is evolutionarily conserved and has been associated with numerous developmental processes, including stem cell maintenance and adult tissue homeostasis. Notably, both abnormal increases and deficiencies of Notch signaling result in human developmental anomalies and...