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Cited by 175Hippo pathway signaling and YAP/TAZCancer-related molecular mechanisms researchMicrotubule and mitosis dynamics

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Assembly and activation of the Hippo signalome by FAT1 tumor suppressor

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Martin, Daniel, Degese, Maria S., Vitale-Cross, Lynn, Iglesias-Bartolome, Ramiro, Valera, Juan Luis Callejas, Wang, Zhiyong, Feng, Xiaodong, Yeerna, Huwate, Vadmal, Vachan, Moroishi, Toshiro, Thorne, Rick F., Zaida, Moraima, Siegele, Bradford, Cheong, Sok C., Molinolo, Alfredo A., Samuels, Yardena, Tamayo, Pablo, Guan, Kun Liang, Lippman, Scott M., Lyons, J. Guy, Gutkind, J. Silvio·2018·Nature Communications
DOI 10.1038/s41467-018-04590-1PMC PMC6037762
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Abstract

Dysregulation of the Hippo signaling pathway and the consequent YAP1 activation is a frequent event in human malignancies, yet the underlying molecular mechanisms are still poorly understood. A pancancer analysis of core Hippo kinases and their candidate regulating molecules revealed few alterations in the canonical Hippo pathway, but very frequent genetic alterations in the FAT family of atypical cadherins. By focusing on head and neck squamous cell carcinoma (HNSCC), which displays frequent FAT1 alterations (29.8%), we provide evidence that FAT1 functional loss results in YAP1 activation. Mechanistically, we found that FAT1 assembles a multimeric Hippo signaling complex (signalome), resulting in activation of core Hippo kinases by TAOKs and consequent YAP1 inactivation. We also show that unrestrained YAP1 acts as an oncogenic driver in HNSCC, and that targeting YAP1 may represent an attractive precision therapeutic option for cancers harboring genomic alterations in the FAT1 tumor suppressor genes.

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Fig. 1 Frequent alterations of FAT1 are linked to YAP1 overactivity in cancer. a Analysis of FAT1 alterations in human malignancies. The significance of FAT1 alterations in a panel of common human malignancies was analyzed by the MUTSIG and GISTIC methods. NS: not significant. See abbreviations and number of cases analyzed for each cancer type in Supplementary Fig. 1. b Graphical representation of cancer types in which FAT1 is most frequently altered. c Analysis of FAT1 mutations in 279 fully characterized HNSCC samples from TCGA. d REVEALER analysis on the TCGA HNSCC RNASeq dataset (n = 504) was used to identify genomic abnormalities that negatively correlate with YAP1 amplification and increased expression of the YAP1 targets CTGF and CYR61. e Enrichment analysis of transcription factor binding sites on upregulated genes in HNSCC samples harboring FAT1 and FAT2 alterations. f YAP1 immunohistochemistry depicting the increase of expression levels and nuclear localization (activation) during HNSCC disease progression. Scale bar upper panels, 100 µm, lower panel, 50 µm. g YAP1 staining quantification. WD, well differentiated; MD, moderately differentiated; PD, poorly differentiated. Bars represent average plus standard error of the mean (SEM). **P < 0.01, ***P < 0.001 (One-way ANOVA)
Fig. 1 Frequent alterations of FAT1 are linked to YAP1 overactivity in cancer. a Analysis of FAT1 alterations in human malignancies. The significance of FAT1 alterations in a panel of common human malignancies was analyzed by the MUTSIG and GISTIC methods. NS: not significant. See abbreviations and number of cases analyzed for each cancer type in Supplementary Fig. 1. b Graphical representation of cancer types in which FAT1 is most frequently altered. c Analysis of FAT1 mutations in 279 fully characterized HNSCC samples from TCGA. d REVEALER analysis on the TCGA HNSCC RNASeq dataset (n = 504) was used to identify genomic abnormalities that negatively correlate with YAP1 amplification and increased expression of the YAP1 targets CTGF and CYR61. e Enrichment analysis of transcription factor binding sites on upregulated genes in HNSCC samples harboring FAT1 and FAT2 alterations. f YAP1 immunohistochemistry depicting the increase of expression levels and nuclear localization (activation) during HNSCC disease progression. Scale bar upper panels, 100 µm, lower panel, 50 µm. g YAP1 staining quantification. WD, well differentiated; MD, moderately differentiated; PD, poorly differentiated. Bars represent average plus standard error of the mean (SEM). **P < 0.01, ***P < 0.001 (One-way ANOVA)CC BY · PubMed Central
Fig. 2 FAT1 regulates YAP1 nuclear localization and activity. a siRNA-mediated knockdown of FAT1 and FAT2 in HEK293 cells induces the accumulation of nuclear YAP1 as depicted by immunofluorescence and its associated quantification. In green (Alexa 488), YAP1 staining and in blue, the nuclear counterstain DAPI. A representative experiment is shown. Scale bar, 25 µm. b Knockdown of FAT1 and FAT2 induces the upregulation of the YAP1 targets CTGF and CYR61 in HEK293 cells in a YAP1-dependent manner. Gene expression analysis of HEK293 cells transiently transfected with siRNAs against control (scrambled), YAP1, FAT1, and FAT2 as indicated. mRNA levels were evaluated by quantitative PCR (qPCR). Bars represent the GAPDH-normalized mean ± SEM (N = 3). c Schematic representation of the CD4-FAT1-ICD chimeric constructs. d Expression and correct plasma membrane localization of the CD4 chimeras by western blot and FACS. Arrows indicate the specific CD4-chimera bands. Predicted molecular weights CD4ext 46 kDa and both CD4-FAT1 91 kDa. e TEAD-Luciferase reporter assay in HEK293 cells stably transfected with the CD4-FAT1 chimeric constructs. Luciferase expression was evaluated in exponentially growing cultures 36 h after transfection. Bars represent mean Renilla-normalized luciferase expression ± SEM (N = 4). f Transient overexpression of CD4ext and CD4-FAT1-TM/ICD induces YAP1 nuclear exclusion in HEK293 cells 24 h after transfection. A representative immunofluorescence is shown. The nuclear or cytoplasmatic localization of YAP1 was visually evaluated in at least 100 transfected CD4 positive cells from three independent experiments and their quantification is shown in the right panel. Bars represent mean proportion ± SEM of the nuclear and cytoplasmatic localization of YAP1. Scale bar, 20 µm. g Quantitative PCR depicting gene expression levels of the YAP1 transcriptional targets CTFG and CYR61 in HEK293 stably expressing CD4-FAT1 ICD constructs. Bars represent the GAPDH-normalized mean ± SEM (N = 3). *P < 0.05, **P < 0.01, ***P < 0.001 (One-way ANOVA)
Fig. 2 FAT1 regulates YAP1 nuclear localization and activity. a siRNA-mediated knockdown of FAT1 and FAT2 in HEK293 cells induces the accumulation of nuclear YAP1 as depicted by immunofluorescence and its associated quantification. In green (Alexa 488), YAP1 staining and in blue, the nuclear counterstain DAPI. A representative experiment is shown. Scale bar, 25 µm. b Knockdown of FAT1 and FAT2 induces the upregulation of the YAP1 targets CTGF and CYR61 in HEK293 cells in a YAP1-dependent manner. Gene expression analysis of HEK293 cells transiently transfected with siRNAs against control (scrambled), YAP1, FAT1, and FAT2 as indicated. mRNA levels were evaluated by quantitative PCR (qPCR). Bars represent the GAPDH-normalized mean ± SEM (N = 3). c Schematic representation of the CD4-FAT1-ICD chimeric constructs. d Expression and correct plasma membrane localization of the CD4 chimeras by western blot and FACS. Arrows indicate the specific CD4-chimera bands. Predicted molecular weights CD4ext 46 kDa and both CD4-FAT1 91 kDa. e TEAD-Luciferase reporter assay in HEK293 cells stably transfected with the CD4-FAT1 chimeric constructs. Luciferase expression was evaluated in exponentially growing cultures 36 h after transfection. Bars represent mean Renilla-normalized luciferase expression ± SEM (N = 4). f Transient overexpression of CD4ext and CD4-FAT1-TM/ICD induces YAP1 nuclear exclusion in HEK293 cells 24 h after transfection. A representative immunofluorescence is shown. The nuclear or cytoplasmatic localization of YAP1 was visually evaluated in at least 100 transfected CD4 positive cells from three independent experiments and their quantification is shown in the right panel. Bars represent mean proportion ± SEM of the nuclear and cytoplasmatic localization of YAP1. Scale bar, 20 µm. g Quantitative PCR depicting gene expression levels of the YAP1 transcriptional targets CTFG and CYR61 in HEK293 stably expressing CD4-FAT1 ICD constructs. Bars represent the GAPDH-normalized mean ± SEM (N = 3). *P < 0.05, **P < 0.01, ***P < 0.001 (One-way ANOVA)CC BY · PubMed Central
Fig. 3 The intracellular domain of FAT1 interacts with and activates the Hippo kinase signalome. a Representative western blots against Hippo pathway components in lysates of exponentially growing HEK293 CD4ext and CD4-FAT1-TM/ICD stable cells. Control, parental HEK293 cell line. b Analysis of YAP1 phosphorylation after transient transfection with CD4 control or CD4-FAT1-TM/ICD chimera in WT or the corresponding CRISPR/Cas9 sgRNA engineered knockout HEK293 cells as indicated. HA-YAP1 immunoprecipitates were analyzed by phos-tag phosphorylation affinity shift electrophoresis and YAP1 western blotting. Retarded (phosphorylated) YAP1 is indicated by arrowheads. A representative blot is shown. c Analysis of YAP1 phosphorylation after transient cotransfection with Flag-YAP1 and CD4 control or CD4-FAT1-TM/ICD chimera in HEK293 cells pretreated with control (C) or TAOK1/2/3 siRNA (TAOKs) as indicated. Flag-YAP1 immunoprecipitates were analyzed by phos-tag electrophoresis and YAP1 western blotting. Retarded (phosphorylated) YAP1 is indicated by arrowheads. A representative blot is shown. d On the left, a scheme depicting the GST fusion proteins indicating the approximate location of functional motifs present in FAT1 and LATS1 and the subsequent GST-pulldown assay. On the right, representative western blots of pulldown experiments using GST fusion proteins and HEK293 total cell lysates. e Summary of mutant FAT1 ICD constructs (PPXY and PDZ binding site) and the depicted deletions and their ability to bind MST1 as assessed by pulldown assay. f siRNA-mediated knockdown on HEK293 of the different components of the Hippo signaling pathway and subsequent GST-FAT1-ICD pulldown on whole cells lysates. g Endogenous FAT1 immunoprecipitation by a monoclonal antibody recognizing is extracellular region. Exponentially growing HEK293 were transfected with FAT1 and FAT2 siRNAs for 48 h and then treated for 2 h at 4 °C with DMSO (−) or the reversible crosslinker DSP (+) prior to cell lysis and immunoprecipitation with anti-FAT1. Representative western blots are shown
Fig. 3 The intracellular domain of FAT1 interacts with and activates the Hippo kinase signalome. a Representative western blots against Hippo pathway components in lysates of exponentially growing HEK293 CD4ext and CD4-FAT1-TM/ICD stable cells. Control, parental HEK293 cell line. b Analysis of YAP1 phosphorylation after transient transfection with CD4 control or CD4-FAT1-TM/ICD chimera in WT or the corresponding CRISPR/Cas9 sgRNA engineered knockout HEK293 cells as indicated. HA-YAP1 immunoprecipitates were analyzed by phos-tag phosphorylation affinity shift electrophoresis and YAP1 western blotting. Retarded (phosphorylated) YAP1 is indicated by arrowheads. A representative blot is shown. c Analysis of YAP1 phosphorylation after transient cotransfection with Flag-YAP1 and CD4 control or CD4-FAT1-TM/ICD chimera in HEK293 cells pretreated with control (C) or TAOK1/2/3 siRNA (TAOKs) as indicated. Flag-YAP1 immunoprecipitates were analyzed by phos-tag electrophoresis and YAP1 western blotting. Retarded (phosphorylated) YAP1 is indicated by arrowheads. A representative blot is shown. d On the left, a scheme depicting the GST fusion proteins indicating the approximate location of functional motifs present in FAT1 and LATS1 and the subsequent GST-pulldown assay. On the right, representative western blots of pulldown experiments using GST fusion proteins and HEK293 total cell lysates. e Summary of mutant FAT1 ICD constructs (PPXY and PDZ binding site) and the depicted deletions and their ability to bind MST1 as assessed by pulldown assay. f siRNA-mediated knockdown on HEK293 of the different components of the Hippo signaling pathway and subsequent GST-FAT1-ICD pulldown on whole cells lysates. g Endogenous FAT1 immunoprecipitation by a monoclonal antibody recognizing is extracellular region. Exponentially growing HEK293 were transfected with FAT1 and FAT2 siRNAs for 48 h and then treated for 2 h at 4 °C with DMSO (−) or the reversible crosslinker DSP (+) prior to cell lysis and immunoprecipitation with anti-FAT1. Representative western blots are shownCC BY · PubMed Central
Fig. 4 YAP1 is required for HNSCC survival and proliferation in vitro and in vivo. a Analysis of FAT1 expression in a panel of epithelial cells, including HNSCC. b Expression of CD4ext and CD4-FAT1-TM/ICD chimera in the HNSCC cell line CAL33 by CD4 FACS analysis. c TEAD-Luciferase reporter assay in CAL33 cells transiently transfected with the CD4-FAT1 chimeric constructs. Luciferase expression was evaluated in exponentially growing cultures 36 h after transfection. Bars represent mean Renilla-normalized luciferase expression ± SEM (N = 4). d Quantitative PCR depicting gene expression levels of the YAP1 transcriptional targets CTFG and CYR61 in CAL33 stably expressing the CD4-FAT1 ICD constructs. Bars represent the GAPDH-normalized mean ± SEM (N = 3). e In vivo xenograft assay. One million CAL33 cells expressing indicated constructs were injected in nu/nu mice. Data points represent mean volume (N = 10 tumors per group) ± SEM. f YAP-rescue experiments. In vivo flank xenograft assay as in (e) using CAL33 expressing CD4-FAT1-TM/ICD and control or the indicated YAP expression vector. Data points represent mean volume (N = 10 tumors per group) ± SEM. g Spheroid formation assay of stable CAL33 shRNA control and YAP1 shRNA cell lines. Representative pictures are shown on top and diameter quantifications (>200 colonies per group) are shown below. Black lines represent mean ± SEM. h CAL33 stably expressing control and YAP1 shRNAs were stimulated with doxycycline for five days (1 µg/ml) and then transfected with a 8xTEAD-luciferase reporter. Renilla-normalized reporter activity is expressed as % of control. Bars represent mean ± SEM (N = 4). i Apoptosis assay by propidium iodide staining of CAL33 cell lines expressing control or YAP1 shRNA after 5d of Doxycycline stimulation. Bars represent mean ± SEM (N = 4). j In vivo xenograft assay. One million cells were injected in nu/nu mice. Animals were fed Doxycycline food (6 g/Kg) ad libitum 24 h h after tumor cell injection for the duration of the experiment. Data points represent mean volume per group (N = 10 tumors) ± SEM. k Representative immunohistochemical stainings of CAL33 tumors from panel (j). In the Cytokeratin 10 (CK10) panels the dotted red line delimits the proliferating front of the tumor. Scale bar, 100 µm. l Automated histological quantification of stainings in (k), bars represent mean ± SEM (N = 3). **P < 0.01, ***P < 0.001 (One-way ANOVA)
Fig. 4 YAP1 is required for HNSCC survival and proliferation in vitro and in vivo. a Analysis of FAT1 expression in a panel of epithelial cells, including HNSCC. b Expression of CD4ext and CD4-FAT1-TM/ICD chimera in the HNSCC cell line CAL33 by CD4 FACS analysis. c TEAD-Luciferase reporter assay in CAL33 cells transiently transfected with the CD4-FAT1 chimeric constructs. Luciferase expression was evaluated in exponentially growing cultures 36 h after transfection. Bars represent mean Renilla-normalized luciferase expression ± SEM (N = 4). d Quantitative PCR depicting gene expression levels of the YAP1 transcriptional targets CTFG and CYR61 in CAL33 stably expressing the CD4-FAT1 ICD constructs. Bars represent the GAPDH-normalized mean ± SEM (N = 3). e In vivo xenograft assay. One million CAL33 cells expressing indicated constructs were injected in nu/nu mice. Data points represent mean volume (N = 10 tumors per group) ± SEM. f YAP-rescue experiments. In vivo flank xenograft assay as in (e) using CAL33 expressing CD4-FAT1-TM/ICD and control or the indicated YAP expression vector. Data points represent mean volume (N = 10 tumors per group) ± SEM. g Spheroid formation assay of stable CAL33 shRNA control and YAP1 shRNA cell lines. Representative pictures are shown on top and diameter quantifications (>200 colonies per group) are shown below. Black lines represent mean ± SEM. h CAL33 stably expressing control and YAP1 shRNAs were stimulated with doxycycline for five days (1 µg/ml) and then transfected with a 8xTEAD-luciferase reporter. Renilla-normalized reporter activity is expressed as % of control. Bars represent mean ± SEM (N = 4). i Apoptosis assay by propidium iodide staining of CAL33 cell lines expressing control or YAP1 shRNA after 5d of Doxycycline stimulation. Bars represent mean ± SEM (N = 4). j In vivo xenograft assay. One million cells were injected in nu/nu mice. Animals were fed Doxycycline food (6 g/Kg) ad libitum 24 h h after tumor cell injection for the duration of the experiment. Data points represent mean volume per group (N = 10 tumors) ± SEM. k Representative immunohistochemical stainings of CAL33 tumors from panel (j). In the Cytokeratin 10 (CK10) panels the dotted red line delimits the proliferating front of the tumor. Scale bar, 100 µm. l Automated histological quantification of stainings in (k), bars represent mean ± SEM (N = 3). **P < 0.01, ***P < 0.001 (One-way ANOVA)CC BY · PubMed Central
Fig. 5 The YAP1 inhibitor Verteporfin (VP) impacts cell survival, proliferation, and tumor growth. a Dose-response experiment for cell viability as determined by the AlamarBlue assay in CAL33 cell subjected to 48 h treatments with VP. Data points represent mean ± SEM (N = 8). b Gene expression determination by quantitative PCR of YAP1 target genes CYR61, CTGF, and FSTL1 after 18 h treatment with 1 µM VP. Bars represent mean ± SEM (N = 4). c Proliferation assay by cell counting of CAL33 cells exposed to vehicle (Control) or 1 µM VP for the times indicated. Data points represent mean ± SEM (N = 4). d Apoptosis assay by propidium iodide staining. Dose-dependent VP-induced apoptosis at 48 h in CAL33 HNSCC cell. Data points represent mean ± SEM (N = 3). e Spheroid formation assay of CAL33 cells treated with VP as indicated for 10 d. Representative pictures are shown on top, and diameter quantifications (>95 colonies per group) are shown below. Black lines represent mean ± SEM. f In vivo tumorigenesis assay in nu/nu mice. One million CAL33 cells were injected s.c. and tumors were allowed to grow until ~100 mm3. Before treatment the animals were randomized so that the mean tumor size per group was as equal as possible between groups at the initiation of treatment. Then VP was injected daily i.p. (50 mg/Kg). Data points represent mean tumor volume ± SEM (N = 10). g Representative immunohistochemical stainings of CAL33 tumors from panel (f). Scale bar, 100 µm. h Automated histological quantification of BrdU staining in (g). Bars represent mean ± SEM (N = 5). i In vivo tumorigenesis assay by oral orthotopic injection in SCID/NOD mice. Fifty thousand CAL33 cells were injected in the tongue, while VP was injected daily i.p. (50 mg/Kg) starting 24 h after implantation for the duration of the experiment. Right panel, representative gross appearance of the tumor lesions at collection time. Left panel, data points represent mean tumor weight ± SEM (N = 10). j Representative immunohistochemical stainings of CAL33 tumors from panel i. Scale bar, 100 µm. k Automated histological quantification of BrdU staining in (j). Bars represent mean ± SEM (N = 5). *P < 0.05, **P < 0.01, ***P < 0.001 (One-way ANOVA). l Scheme depicting the proposed molecular mechanism model, see text for details
Fig. 5 The YAP1 inhibitor Verteporfin (VP) impacts cell survival, proliferation, and tumor growth. a Dose-response experiment for cell viability as determined by the AlamarBlue assay in CAL33 cell subjected to 48 h treatments with VP. Data points represent mean ± SEM (N = 8). b Gene expression determination by quantitative PCR of YAP1 target genes CYR61, CTGF, and FSTL1 after 18 h treatment with 1 µM VP. Bars represent mean ± SEM (N = 4). c Proliferation assay by cell counting of CAL33 cells exposed to vehicle (Control) or 1 µM VP for the times indicated. Data points represent mean ± SEM (N = 4). d Apoptosis assay by propidium iodide staining. Dose-dependent VP-induced apoptosis at 48 h in CAL33 HNSCC cell. Data points represent mean ± SEM (N = 3). e Spheroid formation assay of CAL33 cells treated with VP as indicated for 10 d. Representative pictures are shown on top, and diameter quantifications (>95 colonies per group) are shown below. Black lines represent mean ± SEM. f In vivo tumorigenesis assay in nu/nu mice. One million CAL33 cells were injected s.c. and tumors were allowed to grow until ~100 mm3. Before treatment the animals were randomized so that the mean tumor size per group was as equal as possible between groups at the initiation of treatment. Then VP was injected daily i.p. (50 mg/Kg). Data points represent mean tumor volume ± SEM (N = 10). g Representative immunohistochemical stainings of CAL33 tumors from panel (f). Scale bar, 100 µm. h Automated histological quantification of BrdU staining in (g). Bars represent mean ± SEM (N = 5). i In vivo tumorigenesis assay by oral orthotopic injection in SCID/NOD mice. Fifty thousand CAL33 cells were injected in the tongue, while VP was injected daily i.p. (50 mg/Kg) starting 24 h after implantation for the duration of the experiment. Right panel, representative gross appearance of the tumor lesions at collection time. Left panel, data points represent mean tumor weight ± SEM (N = 10). j Representative immunohistochemical stainings of CAL33 tumors from panel i. Scale bar, 100 µm. k Automated histological quantification of BrdU staining in (j). Bars represent mean ± SEM (N = 5). *P < 0.05, **P < 0.01, ***P < 0.001 (One-way ANOVA). l Scheme depicting the proposed molecular mechanism model, see text for detailsCC BY · PubMed Central

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Authors
Martin, D., Degese, M. S., Vitale-Cross, L., Iglesias-Bartolome, R., Valera, J. L. C., Wang, Z., Feng, X., Yeerna, H., Vadmal, V., Moroishi, T., Thorne, R. F., Zaida, M., Siegele, B., Cheong, S. C., Molinolo, A. A., Samuels, Y., Tamayo, P., Guan, K. L., Lippman, S. M., Lyons, J. G., & Gutkind, J. S.
Affiliations
  • National Institutes of Health (US)
  • University of California San Diego (US)
  • Hunter Cancer Research Alliance (AU)
  • University of Colorado Anschutz (US)
  • University of Malaya (MY)
  • Weizmann Institute of Science (IL)
  • The University of Sydney (AU)
Corresponding author
  • Lippman, Scott M.
  • Gutkind, J. Silvio
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-07-09
Volume
9
Issue
1
Pages
2372-2372
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-04590-1
PMC
PMC6037762
OpenAlex
W2808390504
Cited by
174
References
44
Citations by year
2026: 14 · 2025: 25 · 2024: 22 · 2023: 25 · 2022: 27 · 2021: 20 · 2020: 17 · 2019: 21 · 2018: 3
FWCI
8.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • The University of Malaya Research Repository (University of Malaya) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • NOVA (University of Newcastle Australia) (submittedVersion)
Funders
  • Israel Science Foundation (877/13)
  • National Health and Medical Research Council (1026232)
  • Cancer Council NSW
  • Japan Society for the Promotion of Science (18H02438)
  • National Human Genome Research Institute (R01HG009285)
  • National Cancer Institute (R35CA196878, U24CA194107, U01CA217885, P30CA023100, U24CA248457)
  • National Institute of Dental and Craniofacial Research (R01DE026870, R01DE026644)
  • FP7 Ideas: European Research Council (335377)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
Hippo signaling pathway, FAT1, atypical cadherin, head and neck squamous cell carcinoma, tumor suppressor
MeSH terms
Squamous Cell Carcinoma of Head and Neck, Hippo Signaling Pathway, YAP-Signaling Proteins, Head and Neck Neoplasms, Humans, Phosphoproteins, Proto-Oncogene Proteins, Transcription Factors, Signal Transduction, Cadherins, Hepatocyte Growth Factor, Protein Serine-Threonine Kinases, Adaptor Proteins, Signal Transducing, Gene Knockdown Techniques, HEK293 Cells

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