Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1 and p27^kip1

References

• Farahani E, Patra HK, Jangamreddy JR, Rashedi I, Kawalec M, Rao Pariti RK, Batakis P, Wiechec E. Cell adhesion molecules and their relation to (cancer) cell stemness. Carcinogenesis 2014; 35:747-59; PMID:24531939; http://dx.doi.org/10.1093/carcin/bgu045
   PubMed Web of Science ®Google Scholar
• Wasik AM, Grabarek J, Pantovic A, Cieslar-Pobuda A, Asgari HR, Bundgaard-Nielsen C, Rafat M, Dixon IM, Ghavami S, Los MJ. Reprogramming and carcinogenesis–parallels and distinctions. Intl Rev Cell Mol Biol 2014; 308:167-203; PMID:24411172; http://dx.doi.org/10.1016/B978-0-12-800097-7.00005-1
   PubMed Web of Science ®Google Scholar
• Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003; 100:3983-8; PMID:12629218; http://dx.doi.org/10.1073/pnas.0530291100
   PubMed Web of Science ®Google Scholar
• Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nature Immunol 2004; 5:738-43; PMID:15170211; http://dx.doi.org/10.1038/ni1080
   PubMed Web of Science ®Google Scholar
• Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature 2004; 432:396-401; PMID:15549107; http://dx.doi.org/10.1038/nature03128
   PubMed Web of Science ®Google Scholar
• O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445:106-10; PMID:17122772; http://dx.doi.org/10.1038/nature05372
   PubMed Web of Science ®Google Scholar
• Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM. Identification of pancreatic cancer stem cells. Cancer Res 2007; 67:1030-7; PMID:17283135; http://dx.doi.org/10.1158/0008-5472.CAN-06-2030
   PubMed Web of Science ®Google Scholar
• Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 2007; 104:973-8; PMID:17210912; http://dx.doi.org/10.1073/pnas.0610117104
   PubMed Web of Science ®Google Scholar
• Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005; 65:10946-51; PMID:16322242; http://dx.doi.org/10.1158/0008-5472.CAN-05-2018
   PubMed Web of Science ®Google Scholar
• Hombach-Klonisch S, Paranjothy T, Wiechec E, Pocar P, Mustafa T, Seifert A, Zahl C, Gerlach KL, Biermann K, Steger K, et al. Cancer stem cells as targets for cancer therapy: selected cancers as examples. Archivum Immunol Ther Exp 2008; 56:165-80; PMID:18512024; http://dx.doi.org/10.1007/s00005-008-0023-4
   PubMed Web of Science ®Google Scholar
• Klonisch T, Wiechec E, Hombach-Klonisch S, Ande SR, Wesselborg S, Schulze-Osthoff K, Los M. Cancer stem cell markers in common cancers – therapeutic implications. Trends Mol Med 2008; 14:450-60; PMID:18775674; http://dx.doi.org/10.1016/j.molmed.2008.08.003
   PubMed Web of Science ®Google Scholar
• Jangamreddy JR, Ghavami S, Grabarek J, Kratz G, Wiechec E, Fredriksson BA, Rao Pariti RK, Cieslar-Pobuda A, Panigrahi S, Los MJ. Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells. Biochim Biophy Acta 2013; 1833:2057-69; PMID:23639289; http://dx.doi.org/10.1016/j.bbamcr.2013.04.011
   PubMed Web of Science ®Google Scholar
• Lage H. An overview of cancer multidrug resistance: a still unsolved problem. Cell Mol Life Sci 2008; 65:3145-67; PMID:18581055; http://dx.doi.org/10.1007/s00018-008-8111-5
   PubMed Web of Science ®Google Scholar
• Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008; 27:5497-510; PMID:18794884; http://dx.doi.org/10.1038/onc.2008.245
   PubMed Web of Science ®Google Scholar
• Karamboulas C, Ailles L. Developmental signaling pathways in cancer stem cells of solid tumors. Biochim Biophys Acta 2013; 1830:2481-95; PMID:23196196; http://dx.doi.org/10.1016/j.bbagen.2012.11.008
   PubMed Web of Science ®Google Scholar
• Zhou BP, Hu MC, Miller SA, Yu Z, Xia W, Lin SY, Hung MC. HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. J Biol Chem 2000; 275:8027-31; PMID:10713122; http://dx.doi.org/10.1074/jbc.275.11.8027
   PubMed Web of Science ®Google Scholar
• Nassif NT, Lobo GP, Wu X, Henderson CJ, Morrison CD, Eng C, Jalaludin B, Segelov E. PTEN mutations are common in sporadic microsatellite stable colorectal cancer. Oncogene 2004; 23:617-28; PMID:14724591; http://dx.doi.org/10.1038/sj.onc.1207059
   PubMed Web of Science ®Google Scholar
• Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Ann Rev Cell Dev Biol 2001; 17:615-75; PMID:11687500; http://dx.doi.org/10.1146/annurev.cellbio.17.1.615
   PubMed Web of Science ®Google Scholar
• Vanhaesebroeck B, Waterfield MD. Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 1999; 253:239-54; PMID:10579926; http://dx.doi.org/10.1006/excr.1999.4701
   PubMed Web of Science ®Google Scholar
• Fruman DA, Meyers RE, Cantley LC. Phosphoinositide kinases. Ann Rev Biochem 1998; 67:481-507; PMID:9759495; http://dx.doi.org/10.1146/annurev.biochem.67.1.481
   PubMed Web of Science ®Google Scholar
• Pawson T, Nash P. Protein-protein interactions define specificity in signal transduction. Genes Dev 2000; 14:1027-47; PMID:10809663
   PubMed Web of Science ®Google Scholar
• Ye K. PIKE/nuclear PI 3-kinase signaling in preventing programmed cell death. J Cell Biochem 2005; 96:463-72; PMID:16088938; http://dx.doi.org/10.1002/jcb.20549
   PubMed Web of Science ®Google Scholar
• Martelli AM, Faenza I, Billi AM, Manzoli L, Evangelisti C, Fala F, Cocco L. Intranuclear 3′-phosphoinositide metabolism and Akt signaling: new mechanisms for tumorigenesis and protection against apoptosis? Cell Signal 2006; 18:1101-7; PMID:16516442; http://dx.doi.org/10.1016/j.cellsig.2006.01.011
   PubMed Web of Science ®Google Scholar
• Dillon RL, White DE, Muller WJ. The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer. Oncogene 2007; 26:1338-45; PMID:17322919; http://dx.doi.org/10.1038/sj.onc.1210202
   PubMed Web of Science ®Google Scholar
• Maddika S, Panigrahi S, Wiechec E, Wesselborg S, Fischer U, Schulze-Osthoff K, Los M. Unscheduled Akt-triggered activation of cyclin-dependent kinase 2 as a key effector mechanism of apoptin's anticancer toxicity. Mol Cell Biol 2009; 29:1235-48; PMID:19103742; http://dx.doi.org/10.1128/MCB.00668-08
   PubMed Web of Science ®Google Scholar
• Downward J. PI 3-kinase, Akt and cell survival. Semin Cell Dev Biol 2004; 15:177-82; PMID:15209377; http://dx.doi.org/10.1016/j.semcdb.2004.01.002
   PubMed Web of Science ®Google Scholar
• Los M, Maddika S, Erb B, Schulze-Osthoff K. Switching Akt: from survival signaling to deadly response. BioEssays 2009; 31:492-5; PMID:19319914; http://dx.doi.org/10.1002/bies.200900005
   PubMed Web of Science ®Google Scholar
• Osaki M, Oshimura M, Ito H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 2004; 9:667-76; PMID:15505410; http://dx.doi.org/10.1023/B:APPT.0000045801.15585.dd
   PubMed Web of Science ®Google Scholar
• Liang J, Zubovitz J, Petrocelli T, Kotchetkov R, Connor MK, Han K, Lee JH, Ciarallo S, Catzavelos C, Beniston R, et al. PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med 2002; 8:1153-60; PMID:12244302; http://dx.doi.org/10.1038/nm761
   PubMed Web of Science ®Google Scholar
• Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, Hung MC. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat Cell Biol 2001; 3:245-52; PMID:11231573; http://dx.doi.org/10.1038/35060032
   PubMed Web of Science ®Google Scholar
• Watanabe S, Umehara H, Murayama K, Okabe M, Kimura T, Nakano T. Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells. Oncogene 2006; 25:2697-707; PMID:16407845; http://dx.doi.org/10.1038/sj.onc.1209307
   PubMed Web of Science ®Google Scholar
• Fischer KM, Din S, Gude N, Konstandin MH, Wu W, Quijada P, Sussman MA. Cardiac progenitor cell commitment is inhibited by nuclear Akt expression. Circ Res 2011; 108:960-70; PMID:21350213; http://dx.doi.org/10.1161/CIRCRESAHA.110.237156
   PubMed Web of Science ®Google Scholar
• Gong J, Traganos F, Darzynkiewicz Z. Growth imbalance and altered expression of cyclins B1, A, E, and D3 in MOLT-4 cells synchronized in the cell cycle by inhibitors of DNA replication. Cell Growth Differ 1995; 6:1485-93.
   PubMedGoogle Scholar
• Cieslar-Pobuda A, Back M, Magnusson K, Jain MV, Rafat M, Ghavami S, Nilsson KP, Los MJ. Cell type related differences in staining with pentameric thiophene derivatives. Cytometry Part A 2014; 85:628-35; PMID:24500794; http://dx.doi.org/10.1002/cyto.a.22437
   PubMed Web of Science ®Google Scholar
• Magnusson K, Appelqvist H, Cieślar-Pobuda A, Wigenius J, Karlsson T, Łos MJ, Kågedal B, Jonasson J, Nilsson KPR. Differential vital staining of normal and transformed cells by an anionic conjugated polyelectrolyte. Cytometry Part A 2015; 87(3):262-72:( #14–120, provisionally accepted); PMID:25605326
   PubMed Web of Science ®Google Scholar
• Shiraishi I, Melendez J, Ahn Y, Skavdahl M, Murphy E, Welch S, Schaefer E, Walsh K, Rosenzweig A, Torella D, et al. Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes. Circ Res 2004; 94:884-91; PMID:14988230; http://dx.doi.org/10.1161/01.RES.0000124394.01180.BE
   PubMed Web of Science ®Google Scholar
• Bijur GN, Jope RS. Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase activation. J Neurochem 2003; 87:1427-35; PMID:14713298; http://dx.doi.org/10.1046/j.1471-4159.2003.02113.x
   PubMed Web of Science ®Google Scholar
• Lin Y, Yang Y, Li W, Chen Q, Li J, Pan X, Zhou L, Liu C, Chen C, He J, et al. Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells. Mol Cell 2012; 48:627-40; PMID:23041284; http://dx.doi.org/10.1016/j.molcel.2012.08.030
   PubMed Web of Science ®Google Scholar
• Peltier J, Conway A, Keung AJ, Schaffer DV. Akt increases sox2 expression in adult hippocampal neural progenitor cells, but increased sox2 does not promote proliferation. Stem Cell Dev 2011; 20:1153-61; PMID:21028992; http://dx.doi.org/10.1089/scd.2010.0130
   PubMed Web of Science ®Google Scholar
• Zhu J, Blenis J, Yuan J. Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proc Natl Acad Sci U S A 2008; 105:6584-9; PMID:18451027; http://dx.doi.org/10.1073/pnas.0802785105
   PubMed Web of Science ®Google Scholar
• Evangelisti C, Ricci F, Tazzari P, Chiarini F, Battistelli M, Falcieri E, Ognibene A, Pagliaro P, Cocco L, McCubrey JA, et al. Preclinical testing of the Akt inhibitor triciribine in T-cell acute lymphoblastic leukemia. J Cell Physiol 2011; 226:822-31; PMID:20857426; http://dx.doi.org/10.1002/jcp.22407
   PubMed Web of Science ®Google Scholar
• Chaabane W, User SD, El-Gazzah M, Jaksik R, Sajjadi E, Rzeszowska-Wolny J, Los MJ. Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp 2013; 61:43-58; PMID:23229678; http://dx.doi.org/10.1007/s00005-012-0205-y
   PubMed Web of Science ®Google Scholar
• Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol 2014; 112:24-49; PMID:24211851; http://dx.doi.org/10.1016/j.pneurobio.2013.10.004
   PubMed Web of Science ®Google Scholar
• Badve S, Collins NR, Bhat-Nakshatri P, Turbin D, Leung S, Thorat M, Dunn SE, Geistlinger TR, Carroll JS, Brown M, et al. Subcellular localization of activated AKT in estrogen receptor- and progesterone receptor-expressing breast cancers: potential clinical implications. Am J Pathol 2010; 176:2139-49; PMID:20228224; http://dx.doi.org/10.2353/ajpath.2010.090477
   PubMed Web of Science ®Google Scholar
• Wiechec E. Implications of genomic instability in the diagnosis and treatment of breast cancer. Expert Rev Mol Diagn 2011; 11:445-53; PMID:21545260; http://dx.doi.org/10.1586/erm.11.21
   PubMed Web of Science ®Google Scholar
• Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414:105-11; PMID:11689955; http://dx.doi.org/10.1038/35102167
   PubMed Web of Science ®Google Scholar
• Zhang M, Rosen JM. Stem cells in the etiology and treatment of cancer. Curr Opin Genet Dev 2006; 16:60-4; PMID:16377171; http://dx.doi.org/10.1016/j.gde.2005.12.008
   PubMed Web of Science ®Google Scholar
• Tan S, Ng Y, James DE. Next-generation Akt inhibitors provide greater specificity: effects on glucose metabolism in adipocytes. Biochem J 2011; 435:539-44; PMID:21348862; http://dx.doi.org/10.1042/BJ20110040
   PubMed Web of Science ®Google Scholar
• Chan CK, Jans DA. Using nuclear targeting signals to enhance non-viral gene transfer. Immunol Cell Biol 2002; 80:119-30; PMID:11940112; http://dx.doi.org/10.1046/j.1440-1711.2002.01061.x
   PubMed Web of Science ®Google Scholar