Cited by 1,817PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

The DOI matches its Crossref record; 101 of the 103 references it cites were found in a registry or an index.

The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation

Open access

Mendoza, Michelle C., Er, E. Emrah, Blenis, John·2011·Trends in Biochemical Sciences

DOI 10.1016/j.tibs.2011.03.006PMC PMC3112285

Open this paper in CoChat — free account

Abstract

The Ras-extracellular signal-regulated kinase (Ras-ERK) and phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) signaling pathways are the chief mechanisms for controlling cell survival, differentiation, proliferation, metabolism, and motility in response to extracellular cues. Components of these pathways were among the first to be discovered when scientists began cloning proto-oncogenes and purifying cellular kinase activities in the 1980s. Ras-ERK and PI3K-mTOR were originally modeled as linear signaling conduits activated by different stimuli, yet even early experiments hinted that they might intersect to regulate each other and co-regulate downstream functions. The extent of this cross-talk and its significance in cancer therapeutics are now becoming clear.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.tibs.2011.03.006

Cites

101 of 101 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cell Signaling by Receptor Tyrosine Kinases
Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929
AKT/PKB signaling: navigating downstream
Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
Inhibition of Mutated, Activated BRAF in Metastatic Melanoma
Flaherty, K. T., Puzanov, I., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., O'Dwyer, P. J., Lee, R. J., Grippo, J. F., Nolop, K., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002011 · Cited by 3,103
MAP kinase signalling pathways in cancer
Dhillon, A. S., Hagan, S., Rath, O., & Kolch, W. (2007) · Oncogene · doi:10.1038/sj.onc.1210421 · Cited by 2,995
Serine Phosphorylation of Death Agonist BAD in Response to Survival Factor Results in Binding to 14-3-3 Not BCL-XL
Zha, J., Harada, H., Yang, E., Jockel, J., & Korsmeyer, S. J. (1996) · Cell · doi:10.1016/s0092-8674(00)81382-3 · Cited by 2,578
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M., Attar, N., Sazegar, H., et al. (2010) · Nature · doi:10.1038/nature09626 · Cited by 2,244
Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954
Cell Survival Promoted by the Ras-MAPK Signaling Pathway by Transcription-Dependent and -Independent Mechanisms
Bonni, A., Brunet, A., West, A. E., Datta, S. R., Takasu, M. A., & Greenberg, M. E. (1999) · Science · doi:10.1126/science.286.5443.1358 · Cited by 1,908
COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460

Flagged first, then by citations

Show all 103 references

2 of the 103 references couldn’t be matched to a known paper.

Sorted by citations

Items 301–400 of 1,004

IGFBP3 Modulates Lung Tumorigenesis and Cell Growth through IGF1 Signaling
Wang, Y. A., Sun, Y., Palmer, J. D., Solomides, C., Huang, L., Shyr, Y., Dicker, A. P., & Lü, B. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0390 · Cited by 63
Patient-derived models recapitulate heterogeneity of molecular signatures and drug response in pediatric high-grade glioma
He, C., Xu, K., Zhu, X., Dunphy, P. S., Gudenas, B. L., Lin, W., Twarog, N. R., Hover, L. D., Kwon, C.-H., Kasper, L. H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24168-8 · Cited by 67
Regulation of cell proliferation by ERK and signal-dependent nuclear translocation of ERK is dependent on Tm5NM1-containing actin filaments
Schevzov, G., Kee, A. J., Wang, B., Sequeira, V. B., Hook, J., Coombes, J. D., Lucas, C. A., Stehn, J. R., Musgrove, E. A., Cretu, A., et al. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-10-1453 · Cited by 67
Ras signaling in aging and metabolic regulation
Slack, C. (2017) · Nutrition and Healthy Aging · doi:10.3233/nha-160021 · Cited by 63
EZH2 Methyltransferase Activity Controls Pten Expression and mTOR Signaling during Fear Memory Reconsolidation
Jarome, T. J., Perez, G., Hauser, R. M., Hatch, K. M., & Lubin, F. D. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0538-18.2018 · Cited by 64
CUDC‐907, a novel dual PI3K and HDAC inhibitor, in prostate cancer: Antitumour activity and molecular mechanism of action
Hu, C., Xia, H., Bai, S., Zhao, J., Edwards, H. J., Li, X., Yang, Y., Lyu, J., Wang, G., Zhan, Y., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15281 · Cited by 60
Concurrent Inhibition of IGF1R and ERK Increases Pancreatic Cancer Sensitivity to Autophagy Inhibitors
Stalnecker, C. A., Grover, K. R., Edwards, A. C., Coleman, M. F., Yang, R., DeLiberty, J. M., Papke, B., Goodwin, C. M., Pierobon, M., Petricoin, E. F., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1443 · Cited by 64
Dynamic Modeling and Analysis of the Cross-Talk between Insulin/AKT and MAPK/ERK Signaling Pathways
Arkun, Y. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149684 · Cited by 64
An immediate–late gene expression module decodes ERK signal duration
Uhlitz, F., Sieber, A., Wyler, E., Fritsche‐Guenther, R., Meisig, J., Landthaler, M., Klinger, B., & Blüthgen, N. (2017) · Molecular Systems Biology · doi:10.15252/msb.20177554 · Cited by 60
Somatic double-hit in MTOR and RPS6 in hemimegalencephaly with intractable epilepsy
Pelorosso, C., Françoise Watrin, A., Conti, V., Buhler, E., Gélot, A., Yang, X., Mei, D., McEvoy‐Venneri, J., Manent, J., Cetica, V., et al. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz194 · Cited by 63
K-Ras prenylation as a potential anticancer target
Baranyi, M., Buday, L., & Hegedűs, B. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09902-w · Cited by 62
The effects of mutant Ras proteins on the cell signalome
Takács, T., Kudlik, G., Kurilla, A., Szeder, B., Buday, L., & Vas, V. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09912-8 · Cited by 62
Acquired Resistance to Clinical Cancer Therapy: A Twist in Physiological Signaling
WICKI, A. N., Mandalà, M., Massi, D., Taverna, D., Tang, H., Hemmings, B. A., & Xue, G. (2016) · Physiological Reviews · doi:10.1152/physrev.00024.2015 · Cited by 64
Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer
Li, S., Correia, G. S. D. C., Wang, J., Manochakian, R., Zhao, Y., & Lou, Y. (2023) · Cancers · doi:10.3390/cancers15112899 · Cited by 64
Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia
Cha, J. Y., Wee, J., Jung, J., Jang, Y., Lee, B., Hong, G., Chang, B. C., Choi, Y., Shin, Y. K., Min, H., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1423827112 · Cited by 62
Endometrial Carcinoma
Buhtoiarova, T. N., Brenner, C. A., & Singh, M. (2015) · American Journal of Clinical Pathology · doi:10.1093/ajcp/aqv014 · Cited by 62
The role of an anti-diabetic drug metformin in the treatment of endocrine tumors
Thakur, S., Daley, B., & Kłubo-Gwieździńska, J. (2019) · Journal of Molecular Endocrinology · doi:10.1530/jme-19-0083 · Cited by 66
Combination of PI3K and MEK inhibitors yields durable remission in PDX models of PIK3CA-mutated metaplastic breast cancers
Coussy, F., Botty, R. E., Lavigne, M., Gu, C., Fuhrmann, L., Briaux, A., de Koning, L., Dahmani, A., Montaudon, É., Morisset, L., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-0846-y · Cited by 61
Disrupting cellular memory to overcome drug resistance
Harmange, G., Hueros, R. A. R., Schaff, D. L., Emert, B. L., Saint-Antoine, M., Kim, L. C., Niu, Z., Nellore, S., Fane, M. E., Alicea, G. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41811-8 · Cited by 58
Targeting Therapeutic Liabilities Engendered by PIK3R1 Mutations for Cancer Treatment
Cheung, L. W. T., & Mills, G. B. (2016) · Pharmacogenomics · doi:10.2217/pgs.15.174 · Cited by 62
Protective effects of GPR37 via regulation of inflammation and multiple cell death pathways after ischemic stroke in mice
McCrary, M. R., Jiang, M., Giddens, M. M., Zhang, J., Owino, S., Wei, Z. Z., Zhong, W., Gu, X.-H., Xin, H., Hall, R., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900070r · Cited by 54
Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle
Liang, N., Xu, Z., Furuya, N., Nonaka, R., Yamada, Y., & Arikawa‐Hirasawa, E. (2015) · Matrix Biology · doi:10.1016/j.matbio.2015.08.002 · Cited by 60
PCNA-interacting peptides reduce Akt phosphorylation and TLR-mediated cytokine secretion suggesting a role of PCNA in cellular signaling
Olaisen, C., Müller, R., Nedal, A., & Otterlei, M. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.03.009 · Cited by 63
Dual Inhibition of PI3K-AKT-mTOR- and RAF-MEK-ERK-signaling is synergistic in cholangiocarcinoma and reverses acquired resistance to MEK-inhibitors
Ewald, F., Nörz, D. S., Grottke, A., Hofmann, B. T., Nashan, B., & Jücker, M. (2014) · Investigational New Drugs · doi:10.1007/s10637-014-0149-7 · Cited by 60
Long chain n-3 polyunsaturated fatty acids increase the efficacy of docetaxel in mammary cancer cells by downregulating Akt and PKCε/δ-induced ERK pathways
Chauvin, L., Goupille, C., Blanc, C., Pinault, M., Domingo, I., Guimaraes, C., Bougnoux, P., Chevalier, S., & Mahéo, K. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.01.012 · Cited by 60
Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells
Varin, J., Poulain, L., Hivelin, M., Nusbaum, P., Hubas, A., Laurendeau, I., Lantieri, L. A., Wolkenstein, P., Vidaud, M., Pasmant, É., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7099 · Cited by 60
E Proteins in Lymphocyte Development and Lymphoid Diseases
Belle, I., & Zhuang, Y. (2014) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-405943-6.00004-x · Cited by 59
Multi-level suppression of receptor-PI3K-mTORC1 by fatty acid synthase inhibitors is crucial for their efficacy against ovarian cancer cells
Wagner, R., Stübiger, G., Veigel, D., Wuczkowski, M., Lanzerstorfer, P., Weghuber, J., Karteris, E., Nowikovsky, K., Wilfinger‐Lutz, N., Singer, C. F., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.14591 · Cited by 60
Metastatic triple-negative breast cancer is dependent on SphKs/S1P signaling for growth and survival
Maiti, A., Takabe, K., & Hait, N. C. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.01.021 · Cited by 60
GITR Agonism Enhances Cellular Metabolism to Support CD8+ T-cell Proliferation and Effector Cytokine Production in a Mouse Tumor Model
Sabharwal, S. S., Rosen, D. B., Grein, J., Tedesco, D., Joyce-Shaikh, B., Ueda, R., Semana, M., Bauer, M., Bang, K., Stevenson, C., et al. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0632 · Cited by 60
Combination of KRAS gene silencing and PI3K inhibition for ovarian cancer treatment
Kim, M. J., Lee, S. J., Ryu, J. H., Kim, S. H., Kwon, I. C., & Roberts, T. M. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.12.019 · Cited by 64
The plasticity of pancreatic cancer stem cells: implications in therapeutic resistance
Patil, K., Badrealam, K. F., Akhtar, S., Ahmad, A., & Shahab Uddin, M. S. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-09979-x · Cited by 60
Ran GTPase and Its Importance in Cellular Signaling and Malignant Phenotype
El‐Tanani, M., Nsairat, H., Mishra, V. K., Mishra, Y., Aljabali, A. A. A., Serrano‐Aroca, Á., & Tambuwala, M. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043065 · Cited by 59
Rapamycin Ameliorates Inflammation and Fibrosis in the Early Phase of Cirrhotic Portal Hypertension in Rats through Inhibition of mTORC1 but Not mTORC2
Wang, W., Yan, J., Wang, H., Shi, M., Zhang, M., Yang, W., Peng, C., & Li, H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083908 · Cited by 59
Potential of GPCRs to modulate MAPK and mTOR pathways in Alzheimer’s disease
Franco, R., Martínez‐Pinilla, E., Navarro, G., & Zamarbide, M. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.01.004 · Cited by 61
PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer
Remmerie, M., & Janssens, V. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00462 · Cited by 60
Autism Spectrum Disorder: Signaling Pathways and Prospective Therapeutic Targets
Baranova, J., Dragunas, G., Botelho, M. C. S., Ayub, A. L. P., Bueno-Alves, R., Alencar, R. R., Papaiz, D. D., Sogayar, M. C., Ulrich, H., & Correa, R. G. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00882-7 · Cited by 63
Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X
Schulz, E., Klampfl, P., Holzapfel, S., Janecke, A., Ulz, P., Renner, W., Kashofer, K., Nojima, S., Leitner, A., Zebisch, A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6191 · Cited by 58
Consider the context: Ras/ERK and PI3K/AKT/mTOR signaling outcomes are pituitary cell type-specific
Roof, A. K., & Gutierrez‐Hartmann, A. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.04.019 · Cited by 57
Cellular Stress and General Pathological Processes
Gusev, E. Y., & Zotova, N. V. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190319114641 · Cited by 64
Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways
Vasudevan, H. N., Mazot, P., He, F., & Soriano, P. M. (2015) · eLife · doi:10.7554/elife.07186 · Cited by 66
Rapamycin-Resistant mTOR Activity Is Required for Sensory Axon Regeneration Induced by a Conditioning Lesion
Chen, W., Lu, N., Ding, Y., Wang, Y., Chan, L. T., Wang, X., Gao, X., Jiang, S., & Liu, K. (2016) · eNeuro · doi:10.1523/eneuro.0358-16.2016 · Cited by 59
Suppression of cancer stem-like phenotypes in NCI-H460 lung cancer cells by vanillin through an Akt-dependent pathway
Srinual, S., Pithi Chanvorachote, B., & Pongrakhananon, V. (2017) · International Journal of Oncology · doi:10.3892/ijo.2017.3879 · Cited by 58
The anticancer effects of curcumin via targeting the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway
Tamaddoni, A., Mohammadi, E., Sedaghat, F., Qujeq, D., & As’habi, A. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104798 · Cited by 59
The ubiquitin system: orchestrating cellular signals in non-small-cell lung cancer
Fan, Q., Wang, Q., Cai, R., Yuan, H., & Xu, M. (2020) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-019-0193-6 · Cited by 58
Piperine for treating breast cancer: A review of molecular mechanisms, combination with anticancer drugs, and nanosystems
Quijia, C. R., & Chorilli, M. (2021) · Phytotherapy Research · doi:10.1002/ptr.7291 · Cited by 57
AMP kinase (PRKAA1)
Krishan, S., Richardson, D. R., & Sahni, S. (2014) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2014-202422 · Cited by 57
Exercise mediated protection of diabetic heart through modulation of microRNA mediated molecular pathways
Lew, K. S., Pearson, J. T., Schwenke, D. O., & Katare, R. (2017) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0484-4 · Cited by 57
Molecular targets of metformin antitumor action
Sośnicki, S., Kapral, M., & Węglarz, L. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.04.021 · Cited by 57
High-Throughput Drug Screening of Primary Tumor Cells Identifies Therapeutic Strategies for Treating Children with High-Risk Cancer
Mayoh, C., Mao, J., Xie, J., Tax, G., Chow, S., Cadiz, R., Pazaky, K., Barahona, P., Ajuyah, P., Trebilcock, P., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-3702 · Cited by 56
Maternal separation and early stress cause long‐lasting effects on dopaminergic and endocannabinergic systems and alters dendritic morphology in the nucleus accumbens and frontal cortex in rats
Romano‐López, A., Méndez‐Díaz, M., García‐García, F., Regalado‐Santiago, C., Ruiz‐Contreras, A. E., & Prospero-Garcia, O. E. (2015) · Developmental Neurobiology · doi:10.1002/dneu.22361 · Cited by 57
Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer
Beadnell, T. C., Nassar, K. W., Rose, M. M., Clark, E. G., Danysh, B. P., Hofmann, M.-C. C., Pozdeyev, N. V., & Schweppe, R. E. (2018) · Oncogenesis · doi:10.1038/s41389-017-0015-5 · Cited by 57
Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late
Remmerie, M., & Janssens, V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082380 · Cited by 56
BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells
He, K., Chen, D., Ruan, H., Li, X., Tong, J., Xu, X. M., Zhang, L., & Yu, J. (2016) · Oncotarget · doi:10.18632/oncotarget.10277 · Cited by 56
Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to chemosensitize anaplastic thyroid carcinoma
Milosevic, Z. C., Pešić, M., Stanković, T., Dinić, J., Milovanović, Z., Stojšić, J. M., Džodić, R. R., Tanić, N., & Banković, J. (2014) · Translational research · doi:10.1016/j.trsl.2014.06.005 · Cited by 55
Synergistic anti-tumor effect of 17AAG with the PI3K/mTOR inhibitor NVP-BEZ235 on human melanoma
Calero, R., Morchon, E., Martínez‐Argudo, I., & Serrano, R. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.07.021 · Cited by 52
Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer
Cozzo, A. J., Coleman, M. F., Pearce, J. B., Pfeil, A. J., Etigunta, S. K., & Hursting, S. D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.590192 · Cited by 55
Precision drugging of the MAPK pathway in head and neck cancer
Ngan, H.-L., Law, C. H., Choi, Y. C. Y., Chan, J. Y.-S., & Lui, V. W. Y. (2022) · npj Genomic Medicine · doi:10.1038/s41525-022-00293-1 · Cited by 60
Mechanistic target of rapamycin (mTOR): a potential new therapeutic target for rheumatoid arthritis
Zhang, F., Cheng, T., & Zhang, S. (2023) · Arthritis Research & Therapy · doi:10.1186/s13075-023-03181-w · Cited by 63
KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways
Mondal, K., Posa, M. K., Shenoy, R. P., & Roychoudhury, S. (2024) · Cells · doi:10.3390/cells13141221 · Cited by 58
The AKT/mTOR pathway mediates neuronal protective effects of erythropoietin in sepsis
Wang, G., Ni, Y.-L., Zhou, X., & Zhang, W. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1821-5 · Cited by 54
Bufalin Reverses Resistance to Sorafenib by Inhibiting Akt Activation in Hepatocellular Carcinoma: The Role of Endoplasmic Reticulum Stress
Zhai, B., Hu, F., Yan, H., Zhao, D., Jin, X., Fang, T., Pan, S., Sun, X., & Xu, L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138485 · Cited by 54
Two is better than one; toward a rational design of combinatorial therapy
Chen, S., & Lahav, G. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.07.020 · Cited by 54
Subthalamic Nucleus Deep Brain Stimulation Employs trkB Signaling for Neuroprotection and Functional Restoration
Fischer, D. L., Kemp, C. J., Cole-Strauss, A., Polinski, N. K., Paumier, K. L., Lipton, J. W., Steece‐Collier, K., Collier, T. J., Buhlinger, D. J., & Sortwell, C. E. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2060-16.2017 · Cited by 54
Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis
Cao, N., Liao, T., Liu, J., Fan, Z., Zeng, Q., Zhou, J., Pei, H., Xi, J., He, L., Chen, L., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.316 · Cited by 53
Importance of ERK1/2 in Regulation of Protein Translation during Oocyte Meiosis
Kalous, J., Tětková, A., Kubelka, M., & Šušor, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030698 · Cited by 53
Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Forés-Martos, J., Catalá-López, F., Sánchez-Valle, J., Ibáñez, K., Tejero, H., Palma‐Gudiel, H., Climent, J., Pancaldi, V., Fañanás, L., Arango, C., et al. (2019) · Molecular Autism · doi:10.1186/s13229-019-0262-8 · Cited by 53
LPA Induces Keratinocyte Differentiation and Promotes Skin Barrier Function through the LPAR1/LPAR5-RHO-ROCK-SRF Axis
Sumitomo, A., Siriwach, R., Thumkeo, D., Ito, K., Nakagawa, R., Tanaka, N., Tanabe, K., Watanabe, A., Kishibe, M., Ishida‐Yamamoto, A., et al. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.10.034 · Cited by 53
The myonuclear DNA methylome in response to an acute hypertrophic stimulus
von Walden, F., Rea, M., Mobley, C. B., Fondufe‐Mittendorf, Y. N., McCarthy, J. J., Peterson, C. A., & Murach, K. A. (2020) · Epigenetics · doi:10.1080/15592294.2020.1755581 · Cited by 57
Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast
Madrid, M., Vázquez-Marín, B., Franco, A., Soto, T., Vicente‐Soler, J., Gacto, M., & Cansado, J. (2016) · Scientific Reports · doi:10.1038/srep37515 · Cited by 53
PD‐1‐induced T cell exhaustion is controlled by a Drp1‐dependent mechanism
Simula, L., Antonucci, Y., Scarpelli, G., Cancila, V., Colamatteo, A., Manni, S., Angelis, B. D., Quintarelli, C., Procaccini, C., Matarese, G., et al. (2021) · Molecular Oncology · doi:10.1002/1878-0261.13103 · Cited by 53
Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer
Hutchinson, R. A., Adams, R., McArt, D. G., Salto‐Tellez, M., Jasani, B., & Hamilton, P. W. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0531-z · Cited by 57
Characterization of patient-derived tumor xenograft models of endometrial cancer for preclinical evaluation of targeted therapies
Depreeuw, J., Hermans, E., Schrauwen, S., Annibali, D., Coenegrachts, L., Thomas, D., Luyckx, M., Gutierrez-Roelens, I., Debruyne, D., Konings, K., et al. (2015) · Gynecologic Oncology · doi:10.1016/j.ygyno.2015.07.104 · Cited by 53
IGF1R Derived PI3K/AKT Signaling Maintains Growth in a Subset of Human T-Cell Acute Lymphoblastic Leukemias
Gusscott, S., Jenkins, C. E., Lam, S. H. L., Giambra, V., Pollak, M., & Weng, A. P. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161158 · Cited by 53
PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer
Milella, M., Falcone, I., Conciatori, F., Matteoni, S., Sacconi, A., Luca, T. D., Bazzichetto, C., Corbo, V., Simbolo, M., Sperduti, I., et al. (2017) · Scientific Reports · doi:10.1038/srep43013 · Cited by 53
Translational control of ERK signaling through miRNA/4EHP-directed silencing
Jafarnejad, S. M., Chapat, C., Matta‐Camacho, E., Gelbart, I. A., Hesketh, G. G., Arguello, M., Garzia, A., Kim, S., Attig, J., Shapiro, M., et al. (2018) · eLife · doi:10.7554/elife.35034 · Cited by 50
Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer
Holloway, R. W., & Marignani, P. A. (2021) · Cancers · doi:10.3390/cancers13122922 · Cited by 56
Low‐intensity pulsed ultrasound ameliorates depression‐like behaviors in a rat model of chronic unpredictable stress
Zhang, J., Zhou, H., Yang, J., Jia, J., Niu, L., Sun, Z., Shi, D., Meng, L., Qiu, W., Wang, X., et al. (2020) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13463 · Cited by 51
Oroxylin A induces autophagy in human malignant glioma cells via the mTOR‐STAT3‐Notch signaling pathway
Zou, M., Chen, H., You, Q., Zhang, A., Wang, X., & Guo, Q. (2014) · Molecular Carcinogenesis · doi:10.1002/mc.22212 · Cited by 52
Temporal dynamics of a homeostatic pathway controlling neural network activity
Bateup, H. S., Denefrio, C. L., Johnson, C. A., Saulnier, J. L., & Sabatini, B. L. (2013) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2013.00028 · Cited by 52
miRs-134 and -370 function as tumor suppressors in colorectal cancer by independently suppressing EGFR and PI3K signalling
El‐Daly, S. M., Abba, M. L., Patil, N., & Allgayer, H. (2016) · Scientific Reports · doi:10.1038/srep24720 · Cited by 52
Independent association of PD‐L1 expression with noninactivated VHL clear cell renal cell carcinoma—A finding with therapeutic potential
Kammerer‐Jacquet, S., Crouzet, L., Brunot, A., Dagher, J., Pladys, A., Edeline, J., Laguerre, B., Peyronnet, B., Mathiéu, R., Verhoest, G., et al. (2016) · International Journal of Cancer · doi:10.1002/ijc.30429 · Cited by 52
RAS signalling in energy metabolism and rare human diseases
Dard, L., Bellancé, N., Lacombe, D., & Rossignol, R. (2018) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2018.05.003 · Cited by 56
Hyperglycemia-Induced Aberrant Cell Proliferation; A Metabolic Challenge Mediated by Protein O-GlcNAc Modification
Nagy, T., Fisi, V., Frank, D., Kátai, E., Nagy, Z., & Miseta, A. (2019) · Cells · doi:10.3390/cells8090999 · Cited by 54
Molecular Pathogenesis and Classification of Colorectal Carcinoma
Kasi, A., Handa, S., Bhatti, S. A., Umar, S., Bansal, A. K., & Sun, W. (2020) · Current Colorectal Cancer Reports · doi:10.1007/s11888-020-00458-z · Cited by 56
Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways
Majnooni, M. B., Fakhri, S., Ghanadian, S. M., Bahrami, G., Mansouri, K., Iranpanah, A., Farzaei, M. H., & Mojarrab, M. (2023) · Metabolites · doi:10.3390/metabo13030323 · Cited by 58
Oxidized ATM promotes abnormal proliferation of breast CAFs through maintaining intracellular redox homeostasis and activating the PI3K-AKT, MEK-ERK, and Wnt-β-catenin signaling pathways
Tang, S., Hou, Y., Zhang, H., Tu, G., Yang, L., Sun, Y., Lang, L., Tang, X., Du, Y.-E., Zhou, M., et al. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1041685 · Cited by 53
Enhancing therapeutic efficacy of the MEK inhibitor, MEK162, by blocking autophagy or inhibiting PI3K/Akt signaling in human lung cancer cells
Yao, W.-L., Yue, P., Zhang, G.-J., Owonikoko, T., Khuri, F., & Sun, S.-Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.04.028 · Cited by 51
Quercitrin Stimulates Hair Growth with Enhanced Expression of Growth Factors via Activation of MAPK/CREB Signaling Pathway
Kim, J. J., Kim, S. R., Choi, Y.-H., Shin, J. Y., Kim, C. D., Kang, N., Park, B. C., & Lee, S. (2020) · Molecules · doi:10.3390/molecules25174004 · Cited by 51
The importance of Ras in drug resistance in cancer
Healy, F. M., Prior, I. A., & MacEwan, D. J. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15420 · Cited by 52
Noncanonical TGFβ Pathway Relieves the Blockade of IL1β/TGFβ-Mediated Crosstalk between Tumor and Stroma: TGFBR1 and TAK1 Inhibition in Colorectal Cancer
Guillén Díaz-Maroto, N., Sanz-Pamplona, R., Berdiel-Acer, M., Cimas, F. J., García, E., Gonçalves-Ribeiro, S., Albert, N., Garcia-Vicién, G., Capella, G., Moreno, V., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3957 · Cited by 51
Targeting feedback activation of signaling transduction pathways to overcome drug resistance in cancer
Wang, X., Jiang, W., Du, Y., Dongqi, Z., Zhang, J., Fang, C., Fang, Y., & Chen, Z.-S. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100884 · Cited by 53
Superior efficacy of co-treatment with dual PI3K/mTOR inhibitor NVP-BEZ235 and pan-histone deacetylase inhibitor against human pancreatic cancer
Venkannagari, S., Fiskus, W. C., Peth, K., Atadja, P. W., Hidalgo, M. M., Maitra, A., & Bhalla, K. N. (2012) · Oncotarget · doi:10.18632/oncotarget.724 · Cited by 50
MEK inhibitor trametinib does not prevent the growth of anaplastic lymphoma kinase (ALK)–addicted neuroblastomas
Umapathy, G., Guan, J., Gustafsson, D. E., Javanmardi, N., Cervantes-Madrid, D., Djos, A., Martinsson, T., Palmer, R. H., & Hallberg, B. (2017) · Science Signaling · doi:10.1126/scisignal.aam7550 · Cited by 52
Histone deacetylase inhibitors restore normal hippocampal synaptic plasticity and seizure threshold in a mouse model of Tuberous Sclerosis Complex
Basu, T., O’Riordan, K. J., Schoenike, B. A., Khan, N., Wallace, E. P., Rodriguez, G., Maganti, R. K., & Roopra, A. (2019) · Scientific Reports · doi:10.1038/s41598-019-41744-7 · Cited by 50
Targeting Cancer Stem Cells by Genetically Engineered Chimeric Antigen Receptor T Cells
Alhabbab, R. Y. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00312 · Cited by 51
The MAPK Signaling Cascades
Seger, R., & Wexler, S. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-394447-4.30014-1 · Cited by 50
Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK
Nussinov, R., Yavuz, B. R., Arici, M. K., Demirel, H. C., Zhang, M., Liu, Y., Tsai, C., Jang, H., & Tunçbağ, N. (2023) · Biophysical Reviews · doi:10.1007/s12551-023-01054-9 · Cited by 47
The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons
Rapanelli, M., Frick, L. R., Horn, K. D., Schwarcz, R. C., Pogorelov, V. M., Nairn, A. C., & Pittenger, C. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.731406 · Cited by 46
Niclosamide induces protein ubiquitination and inhibits multiple pro-survival signaling pathways in the human glioblastoma U-87 MG cell line
Cheng, B., Morales, L. D., Zhang, Y., Mito, S., & Tsin, A. T. C. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184324 · Cited by 51

Authors: Mendoza, M. C., Er, E. E., & Blenis, J.
Affiliations: Harvard University (US)
Corresponding author: Blenis, John
ORCID: Mendoza, Michelle C.
Er, E. Emrah
Blenis, John
Venue: Trends in Biochemical Sciences
Publisher: Elsevier BV
Published: 2011-06
Volume: 36
Issue: 6
Pages: 320-328
ISSN: 0968-0004 (ISSN-L)
DOI: 10.1016/j.tibs.2011.03.006
PMC: PMC3112285
OpenAlex: W1998203489
Cited by: 1,817
References: 103
Citations by year: 2026: 112 · 2025: 96 · 2024: 122 · 2023: 133 · 2022: 127 · 2021: 163 · 2020: 166 · 2019: 164 · 2018: 144 · 2017: 158 · 2016: 123 · 2015: 100 · 2014: 92 · 2013: 55 · 2012: 49
FWCI: 5.82
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Biochemical Sciences (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: LAM Foundation
Susan G. Komen
National Cancer Institute (R37CA046595)
National Institute of General Medical Sciences (R01GM051405)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: Ras/ERK signaling pathway, signaling crosstalk, cell survival, cell proliferation, cell differentiation, cellular metabolism, cell motility, proto-oncogenes, cancer therapeutics
MeSH terms: Humans, Signal Transduction, ras Proteins, Extracellular Signal-Regulated MAP Kinases, Phosphatidylinositol 3-Kinase, TOR Serine-Threonine Kinases

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 ›

Are you an author, or do you see a problem with this page? Request a review

The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks