P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3K/AKT and MEK/ERK signaling in breast cancer

Oncogene

Volumn 34, Issue 30, 2015, Pages 3968-3976

  Dillon, L M ^a   Bean, J R ^a   Yang, W ^a   Shee, K ^a   Symonds, L K ^a   Balko, J M ^b   McDonald, W H ^b   Liu, S ^c   Gonzalez Angulo, A M ^c   Mills, G B ^c   Arteaga, C L ^b   Miller, T W ^a,d  

^a DARTMOUTH HITCHCOCK MEDICAL CENTER   (United States)

^b VANDERBILT INGRAM CANCER CENTER   (United States)

^c UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^d DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ERK PROTEIN; ESTROGEN RECEPTOR; MEK PROTEIN; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PIP 3 DEPENDENT RAC EXCHANGE FACTOR 1; PROTEIN KINASE B; RAC1 PROTEIN; SOMATOMEDIN C RECEPTOR; TUMOR MARKER; UNCLASSIFIED DRUG; GROWTH FACTOR RECEPTOR; GUANINE NUCLEOTIDE EXCHANGE FACTOR; PREX1 PROTEIN, HUMAN; RAC PROTEIN;

ANIMAL CELL; ARTICLE; BREAST CANCER; CELL VIABILITY; CONTROLLED STUDY; FEMALE; MCF 7 CELL LINE; MOUSE; NONHUMAN; POSITIVE FEEDBACK; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEPLETION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; ANIMAL; BREAST TUMOR; CANCER TRANSPLANTATION; CELL SURVIVAL; FEEDBACK SYSTEM; HUMAN; METABOLISM; MUTATION; NONOBESE DIABETIC MOUSE; PATHOLOGY; PHYSIOLOGY; SCID MOUSE;

MAMMALIA;

ANIMALS; BREAST NEOPLASMS; CELL SURVIVAL; FEEDBACK, PHYSIOLOGICAL; FEMALE; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HUMANS; MAP KINASE SIGNALING SYSTEM; MCF-7 CELLS; MICE, INBRED NOD; MICE, SCID; MUTATION; NEOPLASM TRANSPLANTATION; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RAC GTP-BINDING PROTEINS; RECEPTORS, GROWTH FACTOR;

EID: 84937967918     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2014.328     Document Type: Article

References (47)

1. Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res 2011; 13: 224.
2. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009; 9: 550-562.
3. Whitman M, Downes CP, Keeler M, Keller T, Cantley L. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 1988; 332: 644-646.
4. Maehama T, Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 1998; 273: 13375-13378.
5. Maira SM, Pecchi S, Huang A, Burger M, Knapp M, Sterker D et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther 2012; 11: 317-328.
6. Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H et al. P-Rex1, a PtdIns(3,4,5)P3-and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac. Cell 2002; 108: 809-821.
7. Qin J, Xie Y, Wang B, Hoshino M, Wolff DW, Zhao J et al. Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis. Oncogene 2009; 28: 1853-1863.
8. Montero JC, Seoane S, Ocana A, Pandiella A. P-Rex1 participates in neuregulin-ErbB signal transduction and its expression correlates with patient outcome in breast cancer. Oncogene 2011; 30: 1059-1071.
9. Sosa MS, Lopez-Haber C, Yang C, Wang H, Lemmon MA, Busillo JM et al. Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer. Mol Cell 2010; 40: 877-892.
10. Fine B, Hodakoski C, Koujak S, Su T, Saal LH, Maurer M et al. Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a. Science 2009; 325: 1261-1265.
11. Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem 2008; 51: 5522-5532.
12. Miller TW, Perez-Torres M, Narasanna A, Guix M, Stal O, Perez-Tenorio G et al. Loss of phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer. Cancer Res 2009; 69: 4192-4201.
13. Chakrabarty A, Sanchez V, Kuba MG, Rinehart C, Arteaga CL. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci USA 2011; 109: 2718-2723.
14. Khatri S, Yepiskoposyan H, Gallo CA, Tandon P, Plas DR. FOXO3a regulates glycolysis via transcriptional control of tumor suppressor TSC1. J Biol Chem 2010; 285: 15960-15965.
15. Creighton CJ, Fu X, Hennessy BT, Casa AJ, Zhang Y, Gonzalez-Angulo AM et al. Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res 2010; 12: R40.
16. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012; 486: 346-352.
17. Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci USA 2007; 104: 7564-7569.
18. Hanker AB, Pfefferle AD, Balko JM, Kuba MG, Young CD, Sanchez V et al. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies. Proc Natl Acad Sci USA 2013; 110: 14372-14377.
19. Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008; 27: 5497-5510.
20. Saini KS, Loi S, de Azambuja E, Metzger-Filho O, Saini ML, Ignatiadis M et al. Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat Rev 2013; 39: 935-946.
21. Wang ZP, Fu M, Wang LF, Liu JJ, Li YH, Brakebusch C et al. P21-activated kinase 1 (PAK1) can promote ERK. J Biol Chem 2013; 288: 20093-20099.
22. King AJ, Sun HY, Diaz B, Barnard D, Miao WY, Bagrodia S et al. The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338. Nature 1998; 396: 180-183.
23. Slack-Davis JK, Eblen ST, Zecevic M, Boerner SA, Tarcsafalvi A, Diaz HB et al. PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J Cell Biol 2003; 162: 281-291.
24. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L. A brain serine threonine proteinkinase activated by Cdc42 and Rac1. Nature 1994; 367: 40-46.
25. Fritsch R, de Krijger I, Fritsch K, George R, Reason B, Kumar MS et al. RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms. Cell 2013; 153: 1050-1063.
26. Yang HW, Shin MG, Lee S, Kim JR, Park WS, Cho KH et al. Cooperative activation of PI3K by Ras and Rho family small GTPases. Mol Cell 2012; 47: 281-290.
27. Onesto C, Shutes A, Picard V, Schweighoffer F, Der CJ. Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. Small Gtpases Dis Part B 2008; 439: 111-129.
28. Hill K, Krugmann S, Andrews SR, Coadwell WJ, Finan P, Welch HC et al. Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits. J Biol Chem 2005; 280: 4166-4173.
29. Hoffman GR, Cerione RA. Signaling to the Rho GTPases: networking with the DH domain. FEBS Lett 2002; 513: 85-91.
30. Hernandez-Negrete I, Carretero-Ortega J, Rosenfeldt H, Hernandez-Garcia R, Calderon-Salinas JV, Reyes-Cruz G et al. P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration. J Biol Chem 2007; 282: 23708-23715.
31. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012; 483: 603-607.
32. O'Brien C, Wallin JJ, Sampath D, GuhaThakurta D, Savage H, Punnoose EA et al. Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models. Clin Cancer Res 2010; 16: 3670-3683.
33. Ebi H, Costa C, Faber AC, Nishtala M, Kotani H, Juric D et al. PI3K regulates MEK/ ERK signaling in breast cancer via the Rac-GEF, P-Rex1. Proc Natl Acad Sci USA 2013; 110: 21124-21129.
34. Guillermet-Guibert J, Bjorklof K, Salpekar A, Gonella C, Ramadani F, Bilancio A et al. The p110 beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110 gamma. Proc Natl Acad Sci USA 2008; 105: 8292-8297.
35. Arias-Romero LE, Villamar-Cruz O, Pacheco A, Kosoff R, Huang M, Muthuswamy SK et al. A Rac-Pak signaling pathway is essential for ErbB2-mediated transformation of human breast epithelial cancer cells. Oncogene 2010; 29: 5839-5849.
36. Premont RT, Perry SJ, Schmalzigaug R, Roseman JT, Xing Y, Claing A. The GIT/PIX complex: An oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors. Cell Signal 2004; 16: 1001-1011.
37. Ong CC, Jubb AM, Haverty PM, Zhou W, Tran V, Truong T et al. Targeting p21-activated kinase 1 (PAK1) to induce apoptosis of tumor cells. Proc Natl Acad Sci USA 2011; 108: 7177-7182.
38. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490: 61-70.
39. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA et al. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012; 2: 401-404.
40. Welch HC, Condliffe AM, Milne LJ, Ferguson GJ, Hill K, Webb LM et al. P-Rex1 regulates neutrophil function. Curr Biol 2005; 15: 1867-1873.
41. Miller TW, Perez-Torres M, Narasanna A, Guix M, Stal O, Perez-Tenorio G et al. Loss of phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer. Cancer Res 2009; 69: 4192-4201.
42. MacCoss MJ, McDonald WH, Saraf A, Sadygov R, Clark JM, Tasto JJ et al. Shotgun identification of protein modifications from protein complexes and lens tissue. Proc Natl Acad Sci USA 2002; 99: 7900-7905.
43. Martinez MN, Emfinger CH, Overton M, Hill S, Ramaswamy TS, Cappel DA et al. Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: A role for ovarian hormones. J Lipid Res 2012; 53: 379-389.
44. Eng JK, McCormack AL, Yates JR III. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J Am Soc Mass Spectrom 1994; 5976-989.
45. Ma ZQ, Dasari S, Chambers MC, Litton MD, Sobecki SM, Zimmerman LJ et al. IDPicker 2. 0: improved protein assembly with high discrimination peptide identification filtering. J Proteome Res 2009; 8: 3872-3881.
46. Li J, Lu Y, Akbani R, Ju Z, Roebuck PL, Liu W et al. TCPA: A resource for cancer functional proteomics data. Nat Methods 2013; 10: 1046-1047.
47. Hu ZY, Fan C, Oh DS, Marron JS, He XP, Qaqish BF et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genom 2006; 7: 96.