FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation

Ahmed, Abdulrzag F; Bock, Charles E. de; Lincz, Lisa F.; Pundavela, Jay; Zouikr, Ihssane; Sontag, Estelle; Hondermarck, Hubert; Thorne, Rick F.

doi:10.1007/s00018-015-1955-6

Cited by 38 publications

(34 citation statements)

References 79 publications

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“…Glioblastomas, colorectal, and head and neck cancers show mutations in FAT genes, members of the cadherin family involved in Hippo signaling [34,35]. Two nonsense FAT1 mutations that we identified in MAC (Table 1) were similar to the ones recently reported in head and neck squamous carcinoma.…”

Section: Discussionsupporting

confidence: 78%

Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma

Panaccione

Zhang

et al. 2017

Oral Oncology

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Background Mucinous adenocarcinoma of the salivary gland (MAC) is a lethal cancer with unknown molecular etiology and a high propensity to lymph node metastasis. Mostly due to its orphan status, MAC remains one of the least explored cancers that lacks cell lines and mouse models that could help translational and pre-clinical studies. Surgery with or without radiation remains the only treatment modality but poor overall survival (10-year, 44%) underscores the urgent need for mechanism-based therapies. Methods We developed the first patient-derived xenograft (PDX) model for pre-clinical MAC studies and a cell line that produces aggressively growing tumors after subcutaneous injection into nude mice. We performed cytogenetic, exome, and proteomic profiling of MAC to identify driving mutations, therapeutic targets, and pathways involved in aggressive cancers based on TCGA database mining and GEO analysis. Results: We identified in MAC KRAS (G13D) and TP53 (R213X) mutations that have been previously reported as drivers in a variety of highly aggressive cancers. Somatic mutations were also found in KDM6A, KMT2D, and other genes frequently mutated in colorectal and other cancers: FAT1, NBEA, RELN, RLP1B, and ZFHX3. Proteomic analysis of MAC implied epigenetic up-regulation of a genetic program involved in proliferation and cancer stem cell maintenance. Conclusion Genomic and proteomic analyses provided the first insight into potential molecular drivers of MAC metastases pointing at common mechanisms of CSC propagation in aggressive cancers. The in vitro/in vivo models that we created should aid in the development and validation of new treatment strategies against MAC.

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Section: Discussionsupporting

confidence: 78%

Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma

Panaccione

Zhang

et al. 2017

Oral Oncology

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“…The 293T cells and PC12 cells were transfected using Lipofectamine 2000 (Invitrogen) according to the manufacturer’s protocol. Based on the protocols developed as previously described (Ahmed et al, 2015), cells were subject to cell number and neurite growth analyses. Recombinant neuritin (hNRN1)-containing (500 ng/mL, His treatment as control) medium was added on day 0 and then replaced with fresh hNRN1-containing media every 2 days for a total of 2 days (SH-SY5Y cells) or 7 days (PC12 cells).…”

Section: Methodsmentioning

confidence: 99%

Neuritin Inhibits Notch Signaling through Interacted with Neuralized to Promote the Neurite Growth

Zhang

Guo

Xiong

et al. 2017

Front. Mol. Neurosci.

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Neuritin plays a key role in neural development and regeneration by promoting neurite outgrowth and synapse maturation. However, the mechanism of neuritin in modulating neurite growth has not been elucidated. Here, using yeast two-hybrid we screened and discovered the interaction of neuritin and neuralized (NEURL1), which is an important regulator that can activate Notch signaling through promoting endocytosis of Notch ligand. And then we identified the interaction of neuritin and neuralized by co-immunoprecipitation (IP) assays, and clarified that neuritin and NEURL1 were co-localized on the cell membrane of SH-SY5Y cells. Moreover, neuritin significantly suppressed Notch ligand Jagged1 (JAG1) endocytosis promoted by NEURL1, and then inhibited the activation of Notch receptor Notch intracellular domain (NICD) and decreased the expression of downstream gene hairy and enhancer of split-1 (HES1). Importantly, the effect of neuritin on inhibiting Notch signaling was rescued by NEURL1, which indicated that neuritin is an upstream and negative regulator of NEURL1 to inhibit Notch signaling through interaction with NEURL1. Notably, recombinant neuritin restored the retraction of neurites caused by activation of Notch, and neurite growth stimulated by neuritin was partially blocked by NEURL1. These findings establish neuritin as an upstream and negative regulator of NEURL1 that inhibits Notch signaling to promote neurite growth. This mechanism connects neuritin with Notch signaling, and provides a valuable foundation for further investigation of neuritin’s role in neurodevelopment and neural plasticity.

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“…Another transcriptional coactivator, TAZ/WWTR1, encoded by the WWTR1 gene, controls organ size and tumor suppression by restricting proliferation and promoting apoptosis [73–75]. It acts as a downstream regulatory target in the Hippo pathway.…”

Section: Introductionmentioning

confidence: 99%

WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer

et al. 2017

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The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo. Studies have confirmed that phosphorylated form of WBP2 can move into nuclei and activate the transcription of estrogen receptor (ER) and progesterone receptor (PR), whose expression were the indicators of breast cancer development, indicating that WBP2 may participate in the progression of breast cancer. Both overexpression of WBP2 and activation of tyrosine phosphorylation upregulate the signal cascades in the cross-regulation of the Wnt and ER signaling pathways in breast cancer. Following the binding of WBP2 to the WW domain region of TAZ which can accelerate migration, invasion and is required for the transformed phenotypes of breast cancer cells, the transformation of epithelial to mesenchymal of MCF10A is activated, suggesting that WBP2 is a key player in regulating cell migration. When WBP2 binds with WWOX, a tumor suppressor, ER transactivation and tumor growth can be suppressed. Thus, WBP2 may serve as a molecular on/off switch that controls the crosstalk between E2, WWOX, Wnt, TAZ, and other oncogenic signaling pathways. This review interprets the relationship between WBP2 and breast cancer, and provides comprehensive views about the function of WBP2 in the regulation of the pathogenesis of breast cancer and endocrine therapy in breast cancer treatment.

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FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation

Cited by 38 publications

References 79 publications

Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma

Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma

Neuritin Inhibits Notch Signaling through Interacted with Neuralized to Promote the Neurite Growth

WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer

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