Disabled-2 (): A Key Regulator of Anti- and Pro-Tumorigenic Pathways

Disabled-2 (), a key adaptor protein in clathrin mediated endocytosis, is implicated in the regulation of key signalling pathways involved in homeostasis, cell positioning and epithelial to mesenchymal transition (EMT). It was initially identified as a tumour suppressor implicated in the initiation of ovarian cancer, but was subsequently linked to many other cancer types. contains key functional domains which allow it to negatively regulate key signalling pathways including the mitogen activated protein kinase (MAPK), wingless/integrated (Wnt) and transforming growth factor beta (TGFβ) pathways. Loss of is primarily associated with activation of these pathways and tumour progression, however this review also explores studies which demonstrate the complex nature of function with pro-tumorigenic effects. A recent strong interest in microRNAs (miRNA) in cancer has identified as a common target. This has reignited an interest in research in cancer. Transcriptomics of tumour associated macrophages (TAMs) has also identified a pro-metastatic role of in the tumour microenvironment. This review will cover the broad depth literature on the tumour suppressor role of , highlighting its complex relationships with different pathways. Furthermore, it will explore recent findings which suggest has a more complex role in cancer than initially thought.