EGFL7: Master regulator of cancer pathogenesis, angiogenesis and an emerging mediator of bone homeostasis.
Guoju HongVincent KuekJiaxi ShiLin ZhouXiaorui HanWei HeJennifer TicknerHeng QiuQiushi WeiJiake XuPublished in: Journal of cellular physiology (2018)
Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion. Dysregulation of Egfl7 has been frequently found in several types of cancers, such as malignant glioma, colorectal carcinoma, oral and oesophageal cancers, gastric cancer, hepatocellular carcinoma, pancreatic cancer, breast cancer, lung cancer, osteosarcoma, and acute myeloid leukemia. In addition, altered expression of miR-126, a microRNA associated with Egfl7, was found to play an important role in oncogenesis. More recently, our study has shown that EGFL7 is expressed in both the osteoclast and osteoblast lineages and promotes endothelial cell activities via extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and integrin signaling cascades, indicative of its angiogenic regulation in the bone microenvironment. Thus, understanding the role of EGFL7 may provide novel insights into the development of improved diagnostics and therapeutic treatment for cancers and skeletal pathological disorders, such as ischemic osteonecrosis and bone fracture healing.
Keyphrases
- growth factor
- endothelial cells
- cell proliferation
- signaling pathway
- acute myeloid leukemia
- bone mineral density
- vascular endothelial growth factor
- papillary thyroid
- bone loss
- transcription factor
- stem cells
- childhood cancer
- cell migration
- bone regeneration
- long non coding rna
- poor prognosis
- squamous cell
- inflammatory response
- tyrosine kinase
- immune response
- epithelial mesenchymal transition
- small molecule
- lymph node metastasis
- amino acid
- allogeneic hematopoietic stem cell transplantation
- young adults
- nuclear factor
- protein protein