Energy Stress Regulates Hippo-YAP Signaling Involving AMPK-Mediated Regulation of Angiomotin-like 1 Protein
Open accessAbstract
Hippo signaling is a tumor-suppressor pathway involved in organ size control and tumorigenesis through the inhibition of YAP and TAZ. Here, we show that energy stress induces YAP cytoplasmic retention and S127 phosphorylation and inhibits YAP transcriptional activity and YAP-dependent transformation. These effects require the central metabolic sensor AMP-activated protein kinase (AMPK) and the upstream Hippo pathway components Lats1/Lats2 and angiomotin-like 1 (AMOTL1). Furthermore, we show that AMPK directly phosphorylates S793 of AMOTL1. AMPK activation stabilizes and increases AMOTL1 steady-state protein levels, contributing to YAP inhibition. The phosphorylation-deficient S793Ala mutant of AMOTL1 showed a shorter half-life and conferred resistance to energy-stress-induced YAP inhibition. Our findings link energy sensing to the Hippo-YAP pathway and suggest that YAP may integrate spatial (contact inhibition), mechanical, and metabolic signals to control cellular proliferation and survival.
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AMPK phosphorylates the Yap regulator Amotl1 on Ser293.
“These include the phosphorylation of the Yap regulator Amotl1 on Ser293 by AMPK (26)”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [26]
The Results section, “AMPK directly phosphorylates AMOTL1 at Ser793,” identifies Ser793—not Ser293—as the site and reports that purified AMPK phosphorylated wild-type AMOTL1 but not the S793A mutant. The cited paper therefore gives a different residue number from the citing sentence. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredGlucose and AMPK are endurance-exercise-related signals that have been linked to YAP/TAZ.
“Endurance exercise-associated signals linked to YAP/TAZ”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as DeRan et al Cell Rep (2014)
The Results section (page not provided) links glucose deprivation and AMPK activation to YAP regulation and reports increased YAP and TAZ phosphorylation after treatment with an AMPK activator. It does not examine endurance exercise or establish that these are endurance-exercise-associated signals. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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Cites
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Regulation of the Hippo-YAP Pathway by Glucose Sensor O-GlcNAcylation
Peng, C., Zhu, Y., Zhang, W., Liao, Q., Chen, Y., Zhao, X., Guo, Q., Shen, P., Zhen, B., Qian, X., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.010 · Cited by 283 · see citing works
YAP/TAZ Signaling as a Molecular Link between Fibrosis and Cancer
Noguchi, S. F., Saito, A., & Nagase, T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113674 · Cited by 280 · see citing works
Regulation of TEAD Transcription Factors in Cancer Biology
Huh, H., Kim, D., Jeong, H.-S., & Park, H. (2019) · Cells · doi:10.3390/cells8060600 · Cited by 259 · see citing works
Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila
Liu, B., Zheng, Y., Yin, F., Yu, J., Silverman, N. S., & Pan, D. (2016) · Cell · doi:10.1016/j.cell.2015.12.029 · Cited by 249 · see citing works
“, 2015), and energy stress (DeRan et al., 2014), it remains a challenge to define the exact physiological contexts in which these biological inputs are employed to regulate Hippo signaling in intact tissues.”
BackgroundThe Hippo Pathway in Liver Homeostasis and Pathophysiology
Driskill, J. H., & Pan, D. (2020) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-030420-105050 · Cited by 232 · see citing works
Zhang, X., Li, Y., Ma, Y., Yang, L., Wang, T., Meng, X., Zong, Z., Sun, X., Hua, X., & Li, H. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0892-2 · Cited by 235 · see citing works
RetractedA combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy
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“Therefore, AMPK activators A769662 and AICAR (an AMP-mimetic) are YAP inhibitors [32-34].”
BackgroundInfluentialYAP/TAZ as therapeutic targets in cancer
Zanconato, F., Battilana, G., Cordenonsi, M., & Piccolo, S. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.05.002 · Cited by 216 · see citing works
“AMPK activation by ICAR or metformin (AMPK agonists used in diabetic patients) downregulates expression of YAP/TAZ target genes[37,39] and reduces the outgrowth of transplanted LATS1/2 double knockout MEFs [37].”
BackgroundYap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth
Cox, A. G., Hwang, K. L., Brown, K., Evason, K. J., Beltz, S., Tsomides, A., O’Connor, K., Galli, G. G., Yimlamai, D., Chhangawala, S., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3389 · Cited by 216 · see citing works
Self-citationEMT: A mechanism for escape from EGFR-targeted therapy in lung cancer
Tulchinsky, E. M., Demidov, O. N., Kriajevska, M. V., Barlev, N. A., & Имянитов, Е. Н. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.10.003 · Cited by 209 · see citing works
Tankyrase Inhibitors Target YAP by Stabilizing Angiomotin Family Proteins
Wang, W., Li, N., Li, X., Tran, M. K., Han, X., & Chen, J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.014 · Cited by 208 · see citing works
“Second, AMOT family proteins have also been shown to activate LATS kinase and suppress YAP/TAZ’s activity in a phosphorylation-dependent manner (DeRan et al., 2014; Paramasivam et al., 2011).”
The Hippo signaling pathway in development and regeneration
Zhong, Z., Jiao, Z., & Yu, F. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113926 · Cited by 204 · see citing works
Dissecting the Dual Role of AMPK in Cancer: From Experimental to Human Studies
Zadra, G., Batista, J. L., & Loda, M. F. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0068 · Cited by 196 · see citing works
“Energy homeostasis maintenance Metabolic/signaling reprogramming AMPK-P ACC1 ACC2 ? mTORC1 (TSC2, Raptor phosphorylation) PFKFB 2/3 Survival/ proliferation (YAP) p21/p27 p53 SREBP/ ChREBP ULK1 Histone H2B HMGR TBC1D1 Lipogenesis FAO Cholesterol synthesis Protein synthesis, HIF1a expression Glucose uptake (GLUT4) ?”
BackgroundInfluentialThe Role of Hippo Pathway in Cancer Stem Cell Biology.
Park, J. H., Shin, J. E., & Park, H. W. (2018) · PubMed Central · doi:10.14348/molcells.2018.2242 · Cited by 195 · see citing works
“AMPK can also directly phosphorylate AMOTL1, which regulates LATS and YAP simultaneously (DeRan et al., 2014).”
BackgroundLncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism
Zheng, X. M., Han, H., Liu, G., Ma, Y., Pan, R., Sang, L., Li, R., Yang, L.-J., Marks, J. R., Wang, W., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201797609 · Cited by 190 · see citing works
“…between YAP and glucose homeostasis, where YAP was phosphorylated and suppressed by AMPK in glucose-starved condition while active YAP promotes glycolysis featured with enhanced glucose uptake and lactate production (DeRan et al , 2014; Gailite et al , 2015; Mo et al , 2015; Wang et al , 2015).”
Integration of Hippo-YAP Signaling with Metabolism
Ibar, C., & Irvine, K. D. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.025 · Cited by 189 · see citing works
“In addition, AMPK can inhibit YAP proteins indirectly by phosphorylating AMOTL1 to promote LATS activation (DeRan et al., 2014).”
BackgroundControl of YAP/TAZ Activity by Metabolic and Nutrient-Sensing Pathways
Santinon, G., Pocaterra, A., & Dupont, S. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.11.004 · Cited by 164 · see citing works
“, in luciferase assays) were inconsistent and depended on the cell line, despite efficient AMPK modulation [32,33].”
BackgroundInfluentialThe Hippo pathway in normal development and cancer
Maugeri‐Saccà, M., & Maria, R. D. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.12.011 · Cited by 165 · see citing works
“Conversely, stimulation by Wnt ligands disassembles the destruction complex, promoting both YAP/TAZ- and β-catenin-mediated gene transcription; v) metabolic pathways promoting YAP/TAZ nuclear localization (mevalonate pathway) or their binding to TEAD factors (glucose metabolism and aerobic glycolysis) (DeRan et al., 2…”
BackgroundYAP/TAZ Activation as a Target for Treating Metastatic Cancer
Warren, J., Xiao, Y., & Lamar, J. M. (2018) · Cancers · doi:10.3390/cancers10040115 · Cited by 168 · see citing works
Control of stem cell renewal and fate by YAP and TAZ
Driskill, J. H., & Pan, D. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00644-5 · Cited by 165 · see citing works
“Cells grown in low glucose show increased Hippo pathway activity and cytoplasmic sequestration of YAP/TAZ 31,199,200 , and YAP is required for liver tumorigenesis driven by high glucose 201 .”
BackgroundHippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism
Ardestani, A. D., Lupše, B., & Maedler, K. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.04.006 · Cited by 156 · see citing works
Osmotic stress‐induced phosphorylation by NLK at Ser128 activates YAP
Hong, A. W., Meng, Z., Yuan, H., Plouffe, S. W., Moon, S., Kim, W., Jho, E., & Guan, K. (2016) · EMBO Reports · doi:10.15252/embr.201642681 · Cited by 156 · see citing works
“For example, energy stress activates AMPK to inhibit YAP via both LATS-dependent and LATS-independent mechanisms [24 – 26], and oxidative stress inhibits YAP activity by activating the Hippo pathway [29].”
Chen, Y.-A., Lu, C.-Y., Cheng, T., Pan, S., Chen, H., & Chang, N. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00060 · Cited by 155 · see citing works
“In addition, the junctionassociated angiomotin (AMOT) family proteins angiomotin (Amot) and angiomotin-like 2 (Amotl2) are essential for Hippo pathway activation and appropriate cell fate specification (27).”
BackgroundMechanoregulation and pathology of YAP/TAZ via Hippo and non‐Hippo mechanisms
Dobrokhotov, O., Samsonov, M., Sokabe, M., & Hirata, H. (2018) · Clinical and Translational Medicine · doi:10.1186/s40169-018-0202-9 · Cited by 150 · see citing works
Cancer signaling, cell/gene therapy, diagnosis and role of nanobiomaterials
Rosic, G. L. (2024) · Advances in Biology & Earth Sciences · doi:10.62476/abes9s11 · Cited by 151 · see citing works
“The YAP-TEAD interaction is prevented by AMPK's direct phosphorylation of YAP at serine 61 and serine 94 (Kim et al ., 2020; Deran et al ., 2014).”
An overview of signaling pathways regulating YAP/TAZ activity
Heng, B. C., Zhang, X., Aubel, D., Bai, Y., Li, X., Yan, W., Fussenegger, M., & Deng, X. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03579-8 · Cited by 140 · see citing works
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“laborators (DeRan et al., 2014) reported that metformin, and its more potent analog phenformin,”
BackgroundMethodInfluentialS1P/S1PR3 axis promotes aerobic glycolysis by YAP/c-MYC/PGAM1 axis in osteosarcoma
Shen, Y., Zhao, S., Wang, S., Pan, X., Zhang, Y., Xu, J., Jiang, Y., Li, H., Zhang, Q., Gao, J., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.12.038 · Cited by 134 · see citing works
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Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways
Heng, B. C., Zhang, X., Aubel, D., Bai, Y., Li, X., Yan, W., Fussenegger, M., & Deng, X. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00735 · Cited by 128 · see citing works
Hippo Signaling in the Ovary: Emerging Roles in Development, Fertility, and Disease
Clark, K. L., George, J. W., Przygrodzka, E., Plewes, M. R., Hua, G., Wang, C., & Davis, J. S. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac013 · Cited by 123 · see citing works
Evolving Lessons on the Complex Role of AMPK in Normal Physiology and Cancer
Dasgupta, B., & Chhipa, R. R. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.11.007 · Cited by 120 · see citing works
MARK4 inhibits Hippo signaling to promote proliferation and migration of breast cancer cells
Arash, E. H., Shiban, A., Song, S., & Attisano, L. (2017) · EMBO Reports · doi:10.15252/embr.201642455 · Cited by 119 · see citing works
“Several AMPK family members have recently been shown to be important regulators of Hippo pathway [18 – 20, 40 Here we show that MARK family members activate a YAP/TAZ responsive luciferase reporter, and concordantly, that MARK4 deletion in breast cancer cells leads to loss of nuclear YAP/TAZ and…”
Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth
Cox, A. G., Tsomides, A., Yimlamai, D., Hwang, K. L., Miesfeld, J. B., Galli, G. G., Fowl, B. H., Fort, M. W., Kimberly, Y., Sullivan, M. R., et al. (2018) · The EMBO Journal · doi:10.15252/embj.2018100294 · Cited by 116 · see citing works
“…a link between glucose concentration and Hippo pathway activity has emerged, wherein glucose deprivation or bioenergetic stress activates AMPK and LATS1/2, which phosphorylate and inactivate Yap (DeRan et al , 2014; Enzo et al , 2015; Gailite et al , 2015; Mo et al , 2015; Wang et al , 2015).”
Self-citationNUAK1 promotes organ fibrosis via YAP and TGF-β/SMAD signaling
Zhang, T., He, X., Caldwell, L., Goru, S. K., Severino, L. U., Tolosa, M. F., Misra, P. S., McEvoy, C. M., Christova, T. Y., Liu, Y., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz4028 · Cited by 115 · see citing works
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“The proposed therapeutic strategies encompass the Type of deregulation Reference Functional relevance Proposed mechanism LATS1 downregulation Zhang J, Oncotarget 2016 [34] Lymph node metastasis, poor prognosis, recurrence in GC patients MST1/2 inactivation Tang Y, Cancer Cell 2020 [99] STRN3 high expression is associa…”
BackgroundInfluentialHippo signalling during development
Davis, J. R., & Tapon, N. (2019) · Development · doi:10.1242/dev.167106 · Cited by 108 · see citing works
“AMPK directly inhibits YAP activity, but it also stabilises AmotL1, which promotes the activity of LATS, further reducing YAP transcription (Deran et al., 2014).”
BackgroundThe YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis
Kovar, H., Bierbaumer, L., & Radic-Sarikas, B. (2020) · Cells · doi:10.3390/cells9040972 · Cited by 107 · see citing works
Role of the Hippo pathway and mechanisms for controlling cellular localization of YAP/TAZ
Kwon, H., Kim, J.-Y., & Jho, E. (2021) · FEBS Journal · doi:10.1111/febs.16091 · Cited by 101 · see citing works
Mediated nuclear import and export of TAZ and the underlying molecular requirements
Kofler, M., Speight, P., Little, D., Ciano‐Oliveira, C. D., Szászi, K., & Kapùs, A. (2018) · Nature Communications · doi:10.1038/s41467-018-07450-0 · Cited by 102 · see citing works
A feed forward loop enforces YAP/TAZ signaling during tumorigenesis
Gill, M. K., Christova, T., Zhang, Y. Y., Gregorieff, A., Zhang, L., Narimatsu, M., Song, S., Xiong, S., Couzens, A. L., Tong, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05939-2 · Cited by 95 · see citing works
Role of YAP/TAZ transcriptional regulators in resistance to anti-cancer therapies
Kim, M. H., & Kim, J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2412-x · Cited by 98 · see citing works
A Potential Role of YAP/TAZ in the Interplay Between Metastasis and Metabolic Alterations
Yamaguchi, H., & Taouk, G. M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00928 · Cited by 100 · see citing works
“It has been demonstrated that YAP/TAZ is inactivated under the low glucose condition or by the inhibition of glycolysis while it is activated in response to high levels of glucose (33, 34, 114, 115).”
BackgroundWang, X., Ha, T., Liu, L., Hu, Y., Kao, R. L., Kalbfleisch, J. H., Williams, D. L., & Li, C. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-017-0036-9 · Cited by 98 · see citing works
Metformin targets a YAP1-TEAD4 complex via AMPKα to regulate CCNE1/2 in bladder cancer cells
Wu, Y., Zheng, Q., Li, Y., Wang, G., Gao, S., Zhang, X., Yan, X., Zhang, X., Xie, J., Wang, Y., et al. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1346-1 · Cited by 97 · see citing works
When Phased without Water: Biophysics of Cellular Desiccation, from Biomolecules to Condensates
Romero-Perez, P. S., Dorone, Y., Flores, E., Sukenik, S., & Boeynaems, S. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00659 · Cited by 95 · see citing works
Multifaceted regulation and functions of YAP/TAZ in tumors (Review)
Liu, H., Du, S., Lei, T., Wang, H., He, X., Tong, R., & Wang, Y. (2018) · Oncology Reports · doi:10.3892/or.2018.6423 · Cited by 94 · see citing works
“In addition, AMPK phosphorylates angiomotin-like 1 (AMOTL1) at Ser 793 and increases AMOTL1 steady-state protein levels, which contributes to YAP inhibition (97).”
BackgroundLladó, V., Nakanishi, Y., Durán, Á., Reina‐Campos, M., Shelton, P. M., Linares, J. F., Yajima, T., Campos, A. R., Aza‐Blanc, P., Leitges, M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.007 · Cited by 98 · see citing works
“This is in keeping with very recently reported evidence demonstrating that the Yap pathway is inhibited by energy stress through AMPK and the phosphorylation of AMOTL1 (DeRan et al., 2014).”
BackgroundHuang, H., Zhang, W., Pan, Y., Gao, Y., Deng, L., Li, F., Li, F., Ma, X., Hou, S., Xu, J., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0449 · Cited by 90 · see citing works
Targeting the Hippo Pathway for Breast Cancer Therapy
Wu, L., & Yang, X. (2018) · Cancers · doi:10.3390/cancers10110422 · Cited by 92 · see citing works
“Moreover, energy stress induced by metformin can activate AMP kinase, which directly phosphorylates AMOTL1 and consequently promotes YAP activity in a LATS-independent way (Figure 1; Table 2) [115,116].”
BackgroundDissecting the role of AMP-activated protein kinase in human diseases
Li, J., Zhong, L., Wang, F., & Zhu, H. (2017) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.12.003 · Cited by 89 · see citing works
Evidence of cancer‐promoting roles for AMPK and related kinases
Monteverde, T., Muthalagu, N., Port, J., & Murphy, D. J. (2015) · FEBS Journal · doi:10.1111/febs.13534 · Cited by 88 · see citing works
“Adding complexity to this picture, AMPK was recently shown by three independent groups to suppress YAP1 activity in response to energetic stress [90-92].”
BackgroundTNFα-YAP/p65-HK2 axis mediates breast cancer cell migration
Gao, Y., Yang, Y., Yuan, F., Huang, J., Xu, W., Mao, B., Yuan, Z., & Bi, W. (2017) · Oncogenesis · doi:10.1038/oncsis.2017.83 · Cited by 87 · see citing works
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Mokhtari, R. B., Ashayeri, N., Baghaie, L., Sambi, M., Satari, K., Baluch, N., Bosykh, D. A., Szewczuk, M. R., & Chakraborty, S. (2023) · Cancers · doi:10.3390/cancers15133468 · Cited by 88 · see citing works
The Hippo signaling pathway provides novel anti-cancer drug targets
Bae, J. S., Kim, S. M., & Lee, H. (2016) · Oncotarget · doi:10.18632/oncotarget.14306 · Cited by 86 · see citing works
“Phosphorylated AMOTL1 promotes YAP-S127 phosphorylation and nuclear exclusion in a Lats kinase-dependent manner [81].”
BackgroundThe posttranslational modifications of Hippo-YAP pathway in cancer
Yan, F., Qian, M., He, Q., Zhu, H., & Yang, B. (2019) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2019.07.006 · Cited by 86 · see citing works
The Hippo Pathway in Prostate Cancer
Salem, O., & Hansen, C. G. (2019) · Cells · doi:10.3390/cells8040370 · Cited by 85 · see citing works
YAP-dependent proliferation by a small molecule targeting annexin A2
Shalhout, S. Z., Yang, P., Grzelak, E. M., Nutsch, K., Shao, S., Zambaldo, C., Iaconelli, J., Ibrahim, L. H., Stanton, C. R., Chadwick, S. R., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00755-0 · Cited by 82 · see citing works
Self-citationAtheroprotective laminar flow inhibits Hippo pathway effector YAP in endothelial cells
Xu, S., Koroleva, M., Yin, M., & Jin, Z. G. (2016) · Translational research · doi:10.1016/j.trsl.2016.05.003 · Cited by 81 · see citing works
The emerging role of Hippo signaling in neurodegeneration
Sahu, M. R., & Mondal, A. C. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24551 · Cited by 80 · see citing works
“Energy stress regulates hippo‐YAP signaling involving AMPK‐mediated regulation of angiomotin‐like 1 protein.”
BackgroundInfluentialWatanabe, Y., Miyasaka, K. Y., Kubo, A., Kida, Y. S., Nakagawa, O., Hirate, Y., Sasaki, H., & Ogura, T. (2017) · Scientific Reports · doi:10.1038/srep46135 · Cited by 80 · see citing works
Regulation of the Hippo pathway in cancer biology
Moon, S., Park, S. Y., & Park, H. W. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2804-1 · Cited by 76 · see citing works
Snaebjornsson, M. T., & Schulze, A. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0065-6 · Cited by 77 · see citing works
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“Previous reports have suggested that AMPK activation stabilizes and increases AMOTL1 steady-state protein levels, contributing to YAP inhibition [42].”
BackgroundUpstairs, downstairs: spatial regulation of Hippo signalling
Fulford, A. D., Tapon, N., & Ribeiro, P. S. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.10.006 · Cited by 71 · see citing works
Angiomotin Family Members: Oncogenes or Tumor Suppressors?
Lv, M., Shen, Y., Yang, J., Li, S., Wang, B., Chen, Z., Liu, P., Liu, P., & Yang, J. (2017) · International Journal of Biological Sciences · doi:10.7150/ijbs.19603 · Cited by 71 · see citing works
“In HEK 293A cells, AMPK stabilizes and increases the levels of Amotl1 steady-state proteins by directly phosphorylating Ser793 of Amotl1, inhibiting cellular proliferation, and increasing survival [64].”
BackgroundSelf-citationA spatiotemporal hypothesis for the regulation, role, and targeting of AMPK in prostate cancer
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“Indeed, atherosclerosis and mitochondrial energy metabolism disorder are cause-and-effect in atherosclerosis (Chiong et al., 2014; Pircher et al., 2016; Dong et al., 2017; Vanhoutte et al., 2017).”
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“44 In addition, metformin can reduce hepatocellular carcinoma cell proliferation by directly phosphorylating YAP1 and reducing its expression through an AMPK-dependent mechanism.”
Dysregulation of the Hippo pathway signaling in aging and cancer
Yeung, Y. T., Guerrero‐Castilla, A., Cano, M., Muñoz, M. F., Ayala, A., & Argüelles, S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.03.018 · Cited by 62 · see citing works
Neuronal Hippo signaling: From development to diseases
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- Authors
- DeRan, M., Yang, J., Shen, C.-H., Peters, E. C., Fitamant, J., Chan, P., Hsieh, M., Zhu, S., Asara, J. M., Zheng, B., Bardeesy, N., Liu, J., & Wu, X.
- Affiliations
- Harvard University (US)
- Genomics Institute of the Novartis Research Foundation (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Wu, Xu
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 9
- Issue
- 2
- Pages
- 495-503
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4223634
- OpenAlex
- W2031354391
- Cited by
- 316
- References
- 36
- Citations by year
- 2026: 22 · 2025: 18 · 2024: 25 · 2023: 30 · 2022: 28 · 2021: 17 · 2020: 40 · 2019: 30 · 2018: 38 · 2017: 21 · 2016: 25 · 2015: 22
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Cancer Institute (R01CA166717, R01CA181537, P01CA120964)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- Hippo signaling pathway, YAP, energy stress, AMPK, AMOTL1, YAP phosphorylation, protein stability, energy sensing, tumor suppression, cell proliferation, contact inhibition, mechanotransduction
- MeSH terms
- Hippo Signaling Pathway, Angiomotins, YAP-Signaling Proteins, Adenylate Kinase, Amino Acid Sequence, Energy Metabolism, Humans, Membrane Proteins, Molecular Sequence Data, Phosphoproteins, Phosphorylation, Stress, Physiological, Transcription Factors, Signal Transduction, Protein Serine-Threonine Kinases, Mutation, Missense, Tumor Suppressor Proteins, Adaptor Proteins, Signal Transducing, Protein Stability, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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