Abstract
The proto-oncogenes YAP and TAZ have previously gained much attention as downstream effectors of Hippo tumour suppressor signalling. While the regulation of YAP/TAZ by MST/LATS kinases is reasonably well understood, the nature of factors functioning upstream of MST/LATS is yet to be elucidated in detail. A recent paper by Ma and co-workers defines a novel role for leukemia inhibitory factor receptor (LIFR) signalling upstream of the Hippo-YAP pathway in breast cancer metastasis. Moreover, a whole genome in vivo RNA interference screen by Lippmann and colleagues identified LIFR as a breast tumour suppressor. Here, we discuss the implications of these studies for breast cancer research and treatment.
Highlights
Hippo signalling is a tumour suppressor cascade highly conserved from yeast to man [1]
The canonical Hippo pathway functions as follows: activated MST1/2 kinases phosphorylate hMOB1 and LATS1/2, resulting in the formation of an active hMOB1-LATS complex that phosphorylates the protooncogenes YAP (Yes-associated protein) and TAZ, which leads to the accumulation of inactive cytoplasmic YAP/TAZ [3]
The articles To uncover novel factors involved in the initiation/ progression of tumours, Lippman and colleagues [12] screened in vivo the entire human genome by RNA interference, thereby identifying leukemia inhibitory factor receptor (LIFR) as a novel tumour suppressor
Summary
Hippo signalling is a tumour suppressor cascade highly conserved from yeast to man [1]. The canonical Hippo pathway functions as follows: activated MST1/2 kinases (mammalian Ste20-like serine/threonine kinase 1/2) phosphorylate hMOB1 (human Mps one binder 1) and LATS1/2 (large tumour suppressor serine/threonine kinase 1/2), resulting in the formation of an active hMOB1-LATS complex that phosphorylates the protooncogenes YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif ), which leads to the accumulation of inactive cytoplasmic YAP/TAZ [3]. YAP is overexpressed in various human cancers [4,5], supporting a role for it as a proto-oncogene.
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