The Phosphoinositide 3-Kinase Pathway

PHOSPHOINOSITIDE KINASES

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Transcription-dependent and -independent control of neuronal survival by the PI3K–Akt signaling pathway

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PKB/Akt

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Regulation of C. elegans Life-Span by Insulinlike Signaling in the Nervous System

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PTEN: a tumour suppressor that functions as a phospholipid phosphatase

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Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells.

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The lipid phosphatase SHIP2 controls insulin sensitivity

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Identification of CISK, a new member of the SGK kinase family that promotes IL-3-dependent survival

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The Redox Regulation of PI 3-Kinase–Dependent Signaling

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Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products

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Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles

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Targeting Apoptosis and Multiple Signaling Pathways with Icariside II in Cancer Cells

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Regulation of Nanog Expression by Phosphoinositide 3-Kinase-dependent Signaling in Murine Embryonic Stem Cells

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Na+,K+-ATPase as a docking station: protein–protein complexes of the Na+,K+-ATPase

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Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST)

Daniels, M., Lurkin, I., Pauli, R., Erbstößer, E., Hildebrandt, U., Hellwig, K., Zschille, U., Lüders, P., Krüger, G., Knolle, J., et al. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.07.029 · Cited by 147

Urinary metabonomics study on biochemical changes in an experimental model of chronic renal failure by adenine based on UPLC Q-TOF/MS

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Energy metabolism of white adipose tissue and insulin resistance in humans

Bódis, K. B., & Roden, M. (2018) · European Journal of Clinical Investigation · doi:10.1111/eci.13017 · Cited by 156

Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-kinase p110delta.

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A “classical” homodimeric erythropoietin receptor is essential for the antiapoptotic effects of erythropoietin on differentiated neuroblastoma SH-SY5Y and pheochromocytoma PC-12 cells

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Lapatinib Antitumor Activity Is Not Dependent upon Phosphatase and Tensin Homologue Deleted on Chromosome 10 in ErbB2-Overexpressing Breast Cancers

Xia, W., Husain, I., Liu, L.-H., Bacus, S. S., Saini, S., Spohn, J., Pry, K. J., Westlund, R. E., Stein, S. H., & Spector, N. L. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2101 · Cited by 147

SIRT6 in DNA repair, metabolism and ageing

Lombard, D. B., Schwer, B., Alt, F. W., & Mostoslavsky, R. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01902.x · Cited by 148

Hypomorphic Mutation of PDK1 Suppresses Tumorigenesis in PTEN+/− Mice

Bayascas, J. R., Leslie, N. R., Parsons, R. E., Fleming, S., & Alessi, D. R. (2005) · Current Biology · doi:10.1016/j.cub.2005.08.066 · Cited by 145

Momordin Ic couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS)-mediated PI3K/Akt and MAPK signaling pathways

Mi, Y., Xiao, C., Du, Q., Wu, W., Qi, G., & Liu, X. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.11.022 · Cited by 145

Synthesis and biological evaluation of pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine derivatives as novel PI3 kinase p110α inhibitors

Hayakawa, M., Kaizawa, H., Moritomo, H., Koizumi, T., Ohishi, T., Yamano, M., Okada, M., Ohta, M., Tsukamoto, S., Raynaud, F. I., et al. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.02.032 · Cited by 145

Semaphorin 4D/Plexin-B1 Induces Endothelial Cell Migration through the Activation of PYK2, Src, and the Phosphatidylinositol 3-Kinase–Akt Pathway

Basile, J. R., Afkhami, T., & Gutkind, J. S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.16.6889-6898.2005 · Cited by 145

Molecular and Cellular Determinants of Skeletal Muscle Atrophy and Hypertrophy

Sartorelli, V., & Fulco, M. (2004) · Science s STKE · doi:10.1126/stke.2442004re11 · Cited by 155

PIK3CAmutation is predictive of poor survival in patients with colorectal cancer

Kato, S., Iida, S., Higuchi, T., Ishikawa, T., Takagi, Y., Yasuno, M., Enomoto, M., Uetake, H., & Sugihara, K. (2007) · International Journal of Cancer · doi:10.1002/ijc.22890 · Cited by 147

Absence of Akt1 Reduces Vascular Smooth Muscle Cell Migration and Survival and Induces Features of Plaque Vulnerability and Cardiac Dysfunction During Atherosclerosis

Fernandez-Hernando, C. F., József, L., Jenkins, D., Lorenzo, A. D., & Sessa, W. C. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.196394 · Cited by 144

Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway in non-small cell lung cancer.

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Cancer-specific mutations in phosphatidylinositol 3-kinase

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Local Phosphatidylinositol 3,4,5-Trisphosphate Accumulation Recruits Vav2 and Vav3 to Activate Rac1/Cdc42 and Initiate Neurite Outgrowth in Nerve Growth Factor-stimulated PC12 Cells

Aoki, K., Nakamura, T., Fujikawa, K., & Matsuda, M. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-10-0904 · Cited by 144

Growth factor receptor cross-talk with estrogen receptor as a mechanism for tamoxifen resistance in breast cancer.

Osborne, C., & Schiff, R. (2003) · Breast · doi:10.1016/s0960-9776(03)00137-1 · Cited by 149

Thyroid Hormone Receptor β1 Acts as a Potent Suppressor of Tumor Invasiveness and Metastasis

Martínez-Iglesias, O. A., Garcı́a-Silva, S., Tenbaum, S. P., Regadera, J., Larcher, F., Paramio, J. M., Vennström, B., & Aranda, A. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2198 · Cited by 145

MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma

Wang, L., Shi, Z., Jiang, C., Liu, X., Chen, Q.-D., Qian, X., Li, D., Ge, X. Q., Wang, X.-F., Liu, L.-Z., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2116 · Cited by 143

PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of DAXX and histone H3.3

Benítez, J. A., Ma, J., D’Antonio, M., Boyer, A. D., Camargo, M. F., Zanca, C., Kelly, S., Khodadadi‐Jamayran, A., Jameson, N. M., Andersen, M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15223 · Cited by 147

Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking

Hou, J. C., & Pessin, J. E. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.04.018 · Cited by 143

Involvement of Insulin/Phosphoinositide 3-Kinase/Akt Signal Pathway in 17β-Estradiol-mediated Neuroprotection

Yu, X., Rajala, R. V. S., McGinnis, J. F., Li, F., Anderson, R. E., Yan, X., Li, S., Elias, R. V., Knapp, R. R., Zhou, X., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313283200 · Cited by 143

Pushing the Envelope in the mTOR Pathway: The Second Generation of Inhibitors

Vilar, E., Pérez-García, J. M., & Tabernero, J. M. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0905 · Cited by 149

Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression

Lindsay, Y. E., McCoull, D., Davidson, L., Leslie, N. R., Fairservice, A., Gray, A., Lucocq, J. M., & Downes, C. P. (2006) · Journal of Cell Science · doi:10.1242/jcs.000133 · Cited by 142

PI3K-Akt-mTOR and MAPK signaling pathways in polycystic ovarian syndrome, uterine leiomyomas and endometriosis: an update

Makker, A., Goel, M. M., Das, V., & Ak, A. (2011) · Gynecological Endocrinology · doi:10.3109/09513590.2011.583955 · Cited by 142

Mechanistic Basis of Differential Cellular Responses of Phosphatidylinositol 3,4-Bisphosphate- and Phosphatidylinositol 3,4,5-Trisphosphate-binding Pleckstrin Homology Domains

Manna, D., Albanese, A., Park, W. S., & Cho, W. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703517200 · Cited by 144

Isoform-selective phosphoinositide 3′-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell–mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach

Niedermeier, M., Hennessy, B. T., Knight, Z. A., Henneberg, M., Hu, J., Kurtova, A. V., Wierda, W. G., Keating, M. J., Shokat, K. M., & Burger, J. A. (2009) · Blood · doi:10.1182/blood-2008-06-165068 · Cited by 142

Tumor‐derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation

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VEGFA Upregulates FLJ10540 and Modulates Migration and Invasion of Lung Cancer via PI3K/AKT Pathway

Chen, C.-H., Lai, J. M., Chou, T. Y., Chen, C., Su, L., Lee, Y.-C., Cheng, T.-S., Hong, Y., Chou, C.-K., Whang‐Peng, J., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005052 · Cited by 141

Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice

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Akt as a therapeutic target in cancer

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Oocyte-Specific Deletion of Pten in Mice Reveals a Stage-Specific Function of PTEN/PI3K Signaling in Oocytes in Controlling Follicular Activation

Jagarlamudi, K., Liu, L., Adhikari, D., Reddy, P., Idahl, A., Ottander, U., Lundin, E., & Liu, K. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006186 · Cited by 141

Quantitative Lipid Imaging Reveals a New Signaling Function of Phosphatidylinositol-3,4-Bisphophate: Isoform- and Site-Specific Activation of Akt

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Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease

Down, K. D., Amour, A., Baldwin, I. T., Cooper, A. W. J., Deakin, A. M., Felton, L. M., Guntrip, S. B., Hardy, C. J., Harrison, Z. A., Jones, K. L., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00767 · Cited by 141

PI3K/Akt signaling as a key regulatory pathway for chondrocyte terminal differentiation

Kita, K., Kimura, T., Nakamura, N., Yoshikawa, H., & Nakano, T. (2008) · Genes to Cells · doi:10.1111/j.1365-2443.2008.01209.x · Cited by 140

Evidence for Down-Regulation of Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR)-Dependent Translation Regulatory Signaling Pathways in Ames Dwarf Mice

Sharp, Z. D., & Bartke, A. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.3.293 · Cited by 122

A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy

Tosch, V., Rohde, H. M., Tronchère, H., Zanoteli, E., Monroy‐Jaramillo, N., Kretz, C., Dondaine, N., Payrastre, B., Mandel, J., & Laporte, J. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl250 · Cited by 150

Highly-expressed micoRNA-21 in adipose derived stem cell exosomes can enhance the migration and proliferation of the HaCaT cells by increasing the MMP-9 expression through the PI3K/AKT pathway

Chen, Y., Luo, L., Bai, X., Shen, K., Liu, K., Wang, J., & Hu, D. (2020) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2020.108259 · Cited by 141

Fenton reaction-based nanomedicine in cancer chemodynamic and synergistic therapy

Meng, X., Zhang, X., Liu, M., Cai, B., He, N., & Wang, Z. (2020) · Applied Materials Today · doi:10.1016/j.apmt.2020.100864 · Cited by 141

p63 and epithelial biology

Barbieri, C. E., & Pietenpol, J. A. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.11.028 · Cited by 146

Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis

Qin, J., Xie, Y., Wang, B., Hoshino, M., Wolff, D. W., Zhao, J., Scofield, M. A., Dowd, F. J., Lin, M.-F., & Tu, Y. (2009) · Oncogene · doi:10.1038/onc.2009.30 · Cited by 139

Posttranslational regulation of Akt in human cancer

Chan, C., Jo, U., Kohrman, A. Q., Rezaeian, A. H., Chou, P.-C., Logothetis, C. J., & Lin, H. (2014) · Cell & Bioscience · doi:10.1186/2045-3701-4-59 · Cited by 143

Akermanite bioceramics promote osteogenesis, angiogenesis and suppress osteoclastogenesis for osteoporotic bone regeneration

Xia, L., Yin, Z., Mao, L., Wang, X., Liu, J., Jiang, X., Zhang, Z., Lin, K., Chang, J., & Fang, B. (2016) · Scientific Reports · doi:10.1038/srep22005 · Cited by 140

Phosphatidylinositol-3-kinase/akt regulates bleomycin-induced fibroblast proliferation and collagen production

Lu, Y., Azad, N., Wang, L., Iyer, A. K. V., Castranova, V., Jiang, B.-H., & Rojanasakul, Y. (2010) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2009-0002oc · Cited by 138

Therapeutic potential of Neurotrophins for repair after brain injury: a helping hand from biomaterials

Houlton, J., Abumaria, N., Hinkley, S. F. R., & Clarkson, A. N. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00790 · Cited by 138

Phosphatidylinositol 3‐phosphate, a lipid that regulates membrane dynamics, protein sorting and cell signalling

Schink, K. O., Raiborg, C., & Stenmark, H. (2013) · BioEssays · doi:10.1002/bies.201300064 · Cited by 150

The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane

Baskin, J. M., Wu, X., Christiano, R., Oh, M. S., Schauder, C. M., Gazzerro, E., Messa, M., Baldassari, S., Assereto, S., Biancheri, R., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3271 · Cited by 144

Airway smooth muscle: A modulator of airway remodeling in asthma

Lazaar, A. L., & Panettieri, R. A. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.06.030 · Cited by 138

Phosphoinositide 3‐kinase controls early and late events in mammalian cell division

García, Z., Kumar, A., Marqués, M., Cortés, I., & Carrera, A. C. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600967 · Cited by 138

FOXO1A Is a Candidate for the 13q14 Tumor Suppressor Gene Inhibiting Androgen Receptor Signaling in Prostate Cancer

Dong, X.-Y., Chen, C., Sun, X., Guo, P., Vessella, R. L., Wang, R.-X., Chung, L. W. K., Zhou, W., & Dong, J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0411 · Cited by 138

Signaling kinases modulated by 4-hydroxynonenal.

Leonarduzzi, G., Robbesyn, F., & Poli, G. (2004) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2004.08.027 · Cited by 143

Metastasis suppressor, NDRG1, mediates its activity through signaling pathways and molecular motors

Sun, J., Zhang, D., Bae, D.-H., Sahni, S., Jansson, P. J., Zheng, Y., Zhao, Q., Yue, F., Zheng, M., Kovačević, Ž., et al. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt163 · Cited by 140

S-palmitoylation of PCSK9 induces sorafenib resistance in liver cancer by activating the PI3K/AKT pathway

Sun, Y., Zhang, H., Meng, J., Guo, F., Ren, D., Wu, H., & Jin, X. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111194 · Cited by 137

Isoform-specific phosphoinositide 3-kinase inhibitors as therapeutic agents

Ward, S. G. (2003) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(03)00078-x · Cited by 139

Integrating differentiation and cancer: The Nkx3.1 homeobox gene in prostate organogenesis and carcinogenesis

Abate-Shen, C. T., Shen, M. M., & Gelmann, E. P. (2008) · Differentiation · doi:10.1111/j.1432-0436.2008.00292.x · Cited by 136

Cancer chemoprevention through the induction of apoptosis by natural compounds

Kuno, T., Tsukamoto, T., Hara, A., & Tanaka, T. (2012) · Journal of Biophysical Chemistry · doi:10.4236/jbpc.2012.32018 · Cited by 136

Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains

Miao, B., Skidan, I. N., Yang, J., Lugovskoy, A. A., Reibarkh, M., Long, K., Brazell, T., Durugkar, K. A., Maki, J. L., Ramana, C. V., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004522107 · Cited by 138

Molecular subtypes and precision treatment of triple-negative breast cancer

Zhao, S., Zuo, W., Shao, Z., & Jiang, Y. (2020) · Annals of Translational Medicine · doi:10.21037/atm.2020.03.194 · Cited by 140

Phospholipase D Couples Survival and Migration Signals in Stress Response of Human Cancer Cells

Yang, Z., Rodrik-Outmezguine, V. S., Toschi, A., Shi, M., Li, H., Shen, Y., & Foster, D. A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600660200 · Cited by 137

Auxin‐induced reactive oxygen species production requires the activation of phosphatidylinositol 3‐kinase

Joo, J. H., Yoo, H. J., Hwang, I., Lee, J. S., Nam, K. H., & Bae, Y. S. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.01.018 · Cited by 136

Phosphoinositide 3-Kinase and Akt Occupy Central Roles in Inflammatory Responses of Toll-Like Receptor 2-Stimulated Neutrophils

Strassheim, D., Asehnoune, K., Park, J.-S., Kim, J. Y., He, Q., Richter, D., Kuhn, K., Mitra, S., & Abraham, E. H. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.9.5727 · Cited by 141

Intracellular Signaling Pathways Regulating Pluripotency of Embryonic Stem Cells

Okita, K., & Yamanaka, S. (2006) · Current Stem Cell Research & Therapy · doi:10.2174/157488806775269061 · Cited by 139

Discovery of (Thienopyrimidin-2-yl)aminopyrimidines as Potent, Selective, and Orally Available Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors for the Treatment of Cancer

Sutherlin, D. P., Sampath, D., Berry, M., Castanedo, G. M., Chang, Z., Chuckowree, I., Dotson, J., Folkes, A. J., Friedman, L. S., Goldsmith, R. A., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm901284w · Cited by 135

Sema4D/plexin‐B1 activates GSK‐3β through R‐Ras GAP activity, inducing growth cone collapse

Ito, Y., Oinuma, I., Katoh, H., Kaibuchi, K., & Negishi, M. (2006) · EMBO Reports · doi:10.1038/sj.embor.7400737 · Cited by 139

Autocrine vascular endothelial growth factor signalling in breast cancer. Evidence from cell lines and primary breast cancer cultures in vitro

Weigand, M., Hantel, P., Kreienberg, R., & Waltenberger, J. L. (2005) · Angiogenesis · doi:10.1007/s10456-005-9010-0 · Cited by 135

Phosphatidylinositol 4-kinase type IIα is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles

Guo, J., Wenk, M. R., Pellegrini, L., Onofri, F., Benfenati, F., & Camilli, P. V. D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0230488100 · Cited by 136

Genetic Alterations of Phosphoinositide 3‐kinase Subunit Genes in Human Glioblastomas

Mizoguchi, M., Nutt, C. L., Mohapatra, G., & Louis, D. N. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00080.x · Cited by 135

Comprehensive genomic analysis of desmoplastic medulloblastomas: identification of novel amplified genes and separate evaluation of the different histological components

Ehrbrecht, A., Müller, U., Wolter, M., Hoischen, A., Koch, A., Radlwimmer, B., Actor, B., Mincheva, A., Pietsch, T., Lichter, P., et al. (2006) · The Journal of Pathology · doi:10.1002/path.1925 · Cited by 135

New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response

Szymonowicz, K., Oeck, S., Malewicz, N. M., & Jendrossek, V. (2018) · Cancers · doi:10.3390/cancers10030078 · Cited by 135

Oxidative Stress in Methylmercury-Induced Cell Toxicity

dos Santos, A. A., Ferrer, B., Gonçalves, F. M., Tsatsakis, A. M., Renieri, E. A., Skalny, A. V., Farina, M., da Rocha, J. B. T., & Aschner, M. (2018) · Toxics · doi:10.3390/toxics6030047 · Cited by 136

Mitochondrial Calcium Regulation of Redox Signaling in Cancer

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The relative role of PLCβ and PI3Kγ in platelet activation

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