The ubiquitin E3 ligase ITCH enhances breast tumor progression by inhibiting the Hippo tumor suppressor pathway

dc.contributor.authorSalah, Zaidoun
dc.contributor.authorItzhaki, Ella
dc.contributor.authorAqeilan, Rami I.
dc.date.accessioned2018-09-16T08:03:45Z
dc.date.available2018-09-16T08:03:45Z
dc.date.issued2014-10-11
dc.description.abstractThe Hippo kinase pathway is emerging as a conserved signaling pathway that is essential for organ growth and tumorigenesis. Recently, we reported that the ubiquitin E3 ligase ITCH negatively regulates LATS1, thereby increasing YAP activity, which leads to increased cell proliferation and decreased apoptosis. Here, we investigated the role of ITCH in breast tumorigenesis. In particular, we show that ITCH enhances epithelial-to-mesenchymal transition (EMT) through boosting YAP oncogenic function. By contrast, a point mutation in the catalytic domain or WW1 domain of ITCH abolished its EMT-mediated effects. Furthermore, while overexpression of ITCH expression in breast cells is associated with increased incidence of mammary tumor formation and progression, its knockdown inhibited breast cancer cell tumorigenicity and metastasis. Importantly, YAP knockdown was able to attenuate ITCH pro-tumorigenic functions. Lastly, we found that ITCH expression is significantly upregulated in invasive and metastatic breast cancer cases and is associated with worse survival. Together, our results reveal that ITCH pro-tumorigenic functions in breast cancer are mediated, at least in part, through inactivation of the Hippo tumor suppressor pathway.en_US
dc.description.sponsorshipWe would like to thank all the Aqeilan lab members for fruitful discussion and technical help. This work was supported by grant funds from the Israel Science Foundation (ISF 12-0542) to R.I.A.en_US
dc.identifier.issn1949-2553
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/904
dc.language.isoen_USen_US
dc.publisherImpact Journalsen_US
dc.titleThe ubiquitin E3 ligase ITCH enhances breast tumor progression by inhibiting the Hippo tumor suppressor pathwayen_US
dc.typeArticleen_US
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