Epidermal Growth Factor-Like Domain Function in Cancer Angiogenesis

The epidermal growth factor-like (EGFL) domain is a structural motif found in a family of secreted extracellular matrix proteins, notably EGFL7 and EGFL6, that orchestrate the formation and remodelling of tumour blood vessels. By interacting with endothelial cell receptors and matrix components, these proteins regulate endothelial proliferation, migration and survival, thereby shaping the vascular network that supplies oxygen and nutrients to growing tumours. Aberrant EGFL signalling contributes to pathological angiogenesis in a range of malignancies, from colorectal and hepatocellular carcinoma to glioblastoma and ovarian cancer. Understanding the dual roles of EGFL domains—in promoting vessel sprouting and in modulating inflammatory cell infiltration—has revealed new therapeutic opportunities to target the tumour vasculature and overcome resistance to established anti-angiogenic agents.

Research from Nature Portfolio

Recent studies have revisited the prognostic and mechanistic importance of EGFL7 in colorectal cancer. In a large clinical cohort, tumours with low intratumoural expression of EGFL7 were associated with increased lymphatic invasion and nodal spread, concurrent with upregulation of VEGFR2 and activation of MAPK and PI3K–Akt pathways, suggesting that loss of EGFL7 may paradoxically favour a more invasive angiogenic phenotype. In metastatic colorectal cancer managed with chemotherapy plus an anti-VEGF antibody, baseline circulating levels of EGFL7 were shown to predict progression-free and overall survival, with higher levels correlating with poorer outcomes. These observations indicate that EGFL7 influences both tumour vascular plasticity and patient response to anti-angiogenic therapy.

Epidermal Growth Factor-Like Domain Function in Cancer Angiogenesis publication trend

The graph below shows the total number of articles in epidermal growth factor-like domain function in cancer angiogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Angiogenesis: Formation of new blood vessels from existing vasculature, critical for tumour growth and metastasis.

EGFL7: Secreted extracellular matrix protein containing epidermal growth factor-like domains, modulates endothelial cell activation and vessel formation.

EGFL6: Related secreted protein with EGF-like domains, implicated in tumour vascular development and cancer cell motility.

Integrin α5β1: Heterodimeric cell-surface receptor binding fibronectin, regulates endothelial adhesion and angiogenic sprouting.

EGFR–AKT signalling: Cell survival and migration pathway initiated by epidermal growth factor receptor activation, contributing to angiogenesis and tumour progression.

References

1. Low EGFL7 expression is associated with high lymph node spread and invasion of lymphatic vessels in colorectal cancer. Scientific Reports (2023).
2. Prognostic importance of circulating epidermal growth factor-like domain 7 in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab. Scientific Reports (2017).
3. Novel role for epidermal growth factor‐like domain 7 in metastasis of human hepatocellular carcinoma. Hepatology (2009).
4. EGFL7 enhances surface expression of integrin α5β1 to promote angiogenesis in malignant brain tumors. EMBO Molecular Medicine (2018).
5. miR-6086 inhibits ovarian cancer angiogenesis by downregulating the OC2/VEGFA/EGFL6 axis. Cell Death & Disease (2020).