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Reciprocal Regulation of Hippo and WBP2 Signalling-Implications in Cancer Therapy.

ABSTRACT: Cancer is a global health problem. The delineation of molecular mechanisms pertinent to cancer initiation and development has spurred cancer therapy in the form of precision medicine. The Hippo signalling pathway is a tumour suppressor pathway implicated in a multitude of cancers. Elucidation of the Hippo pathway has revealed an increasing number of regulators that are implicated, some being potential therapeutic targets for cancer interventions. WW domain-binding protein 2 (WBP2) is an oncogenic transcriptional co-factor that interacts, amongst others, with two other transcriptional co-activators, YAP and TAZ, in the Hippo pathway. WBP2 was recently discovered to modulate the upstream Hippo signalling components by associating with LATS2 and WWC3. Exacerbating the complexity of the WBP2/Hippo network, WBP2 itself is reciprocally regulated by Hippo-mediated microRNA biogenesis, contributing to a positive feedback loop that further drives carcinogenesis. Here, we summarise the biological mechanisms of WBP2/Hippo reciprocal regulation and propose therapeutic strategies to overcome Hippo defects in cancers through targeting WBP2.

SUBMITTER: Lim YX

PROVIDER: S-EPMC8625973 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Regulation of Hippo signalling by p38 signalling.

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Hippo/MST blocks breast cancer by downregulating WBP2 oncogene expression via miRNA processor Dicer.

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Fak-Mapk, Hippo and Wnt signalling pathway expression and regulation in distraction osteogenesis.

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Oncogene-dependent regulation of tumor cells via stromal reciprocal signalling

Project description:Cancer is a heterocellular disease composed of tumor cells and stromal cells. Although stromal cells are known to regulate cancer progression, oncogene-dependent signalling through heterocellular cancer systems remains poorly elucidated. Here, we describe KRASG12D-dependent ‘reciprocal’ signalling across tumor and stromal Pancreatic Ductal Adenocarcinoma (PDA) cells. Heterocellular multivariate phosphoproteomics demonstrates how an oncogenic cue (KRASG12D), a trans-cellular signal (SHH), and stromal cells drive a reciprocal response in tumor cells. KRASG12D-dependent reciprocal signalling regulates the tumor cell phosphoproteome, total proteome, and mitochondria activity via an IGFR1/AXL-AKT axis. The reciprocal KRASG12D signalling state requires a heterocellular context and is unreachable by cell-autonomous oncogenic KRAS alone. These findings provide evidence that oncogenic KRAS regulates tumor cells via heterocellular reciprocation. Comparison between FACS resolved iKRAS cells (previously in co-culture with PSCs) pertubed with a SHH antibody

2015-06-27 | E-GEOD-70351 | biostudies-arrayexpress

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