There are four Notch receptors (Notch1-4) and five ligands. Notch signaling is an evolutionarily conserved pathway that controls cell fate determination, cellular differentiation, and pattern formation in many tissue types by ligand-receptor interactions with neighboring cells.

Adhesion molecules and their role in cancer metastasis. Many adhesion molecules, such as those from the integrin or cadherin family, participate in the attachment process of tumor cells and have been reported to facilitate growth and transmigration of tumor cells ( 5 5. The adhesion of circulating tumor cells to vascular endothelial cells is one of the key steps for metastasis because it can protect tumor cells from anoikis, fluid shear force, and attack from the immune system ( 5 5. The pathogenesis of cancer metastasis: the вЂseed and soilвЂ™ hypothesis revisited. In fact, the circulation system is such a tough environment that only 0.01% of the circulating tumor cells can survive to produce metastasis ( 4 4. Distinct mechanisms of tumor invasion and metastasis.

The tumor cells must overcome numerous hurdles to successfully colonize in the target organ ( 3 3. Tumor metastasis is a complex process that includes local invasion, intravasation, and survival in the circulation, extravasation, and colonization. Metastasis: recent discoveries and novel treatment strategies. The lungs are the most common site of metastasis in melanoma ( 2 2. Therapy for metastatic melanoma: the past, present, and future. Although metastasis only occurs in approximately 10% of melanoma patients, it remains the major cause of death ( 1 1. Metastasis is the key factor in determining the stage, relevant treatment, and prognosis of most solid cancers. These data suggested that Notch ligand Dll1 may enhance the adhesion and metastasis of melanoma cells by upregulation of N-cadherin.Дelta-like 1 Notch signaling Melanoma Metastasis Adhesion N-cadherin Along with increased Dll1 expression, N-cadherin, but not E-cadherin, was upregulated in B16-Dll1 cells. B16-Dll1 cells also had a higher metastatic potential than their counterpart in the mouse model of lung metastasis. Dll1 overexpression activated Notch signaling in B16 tumor cells and significantly enhanced the adhering capacity of B16 tumor cells both in vitro and in vivo. In this article, we extended our study to investigate the effects of Dll1 on tumor cell adhesion and metastasis. Previous research by our group indicated that Notch ligand Delta-like 1 (Dll1) is involved in angiogenesis in melanoma, and we noticed that it took a longer time to trypsinize Dll1-expressing B16 melanoma cells than the control cells. Notch signaling plays a vital role in tumorigenicity and tumor progression by regulating proliferation, invasion, and the tumor microenvironment. ShanДepartment of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China About the authors

FanДepartment of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China L.Q. ZhouДepartment of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China Q.Y. MaДepartment of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China Y. QiuДepartment of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China B.A.

These authors contributed equally to this study.Дepartment of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, ChinaДepartment of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China X.C. Department of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China

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