Rac1 is crucial for Ras-dependent skin tumor formation by controlling Pak1-Mek-Erk hyperactivation and hyperproliferation in vivo

Oncogene

Volumn 29, Issue 23, 2010, Pages 3362-3373

  Wang, Z ^a,b   Pedersen, E ^a   Basse, A ^a   Lefever, T ^a,c   Peyrollier, K ^a   Kapoor, S ^a   Mei, Q ^b   Karlsson, R ^a   Chrostek Grashoff, A ^d   Brakebusch, C ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b FOURTH MILITARY MEDICAL UNIVERSITY   (China)

^c GHENT UNIVERSITY   (Belgium)

^d UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Pak; Rac1; Tumor

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE 1; P21 ACTIVATED KINASE 1; RAC1 PROTEIN; RAS PROTEIN; SERINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVATION; GENE DELETION; IN VITRO STUDY; IN VIVO STUDY; KERATINOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SKIN TUMOR;

9,10-DIMETHYL-1,2-BENZANTHRACENE; ANIMALS; CELL PROLIFERATION; CELLS, CULTURED; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; GENES, RAS; KERATINOCYTES; MICE; MICE, INBRED C57BL; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; NEUROPEPTIDES; P21-ACTIVATED KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RAC GTP-BINDING PROTEINS; SKIN NEOPLASMS; TETRADECANOYLPHORBOL ACETATE;

MUS;

EID: 77953480305     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2010.95     Document Type: Article

References (24)

1. Benitah SA, Frye M, Glogauer M, Watt FM. (2005). Stem cell depletion through epidermal deletion of Rac1. Science 309: 933-935.
2. Castilho RM, Squarize CH, Patel V, Millar SE, Zheng Y, Molinolo A et al. (2007). Requirement of Rac1 distinguishes follicular from interfollicular epithelial stem cells. Oncogene 26: 5078-5085.
3. Chrostek A, Wu X, Quondamatteo F, Hu R, Sanecka A, Jay S et al. (2006). Rac1 is crucial for hair follicle integrity but is not essential for maintenance of the epidermis. Mol Cell Biol 26: 6957-6970.
4. Eblen ST, Slack JK, Weber MJ, Catling AD. (2002). Rac-PAK signaling stimulates extracellular signal-regulated kinase (ERK) activation by regulating formation of MEK1-ERK complexes. Mol Cell Biol 22: 6023-6033.
5. Espina C, Cespedes MV, Garca-Cabezas MA, Gomez del Pulgar MT, Boluda A, Oroz LG et al. (2008). A critical role for Rac1 in tumor progression of human colorectal adenocarcinoma cells. Am J Pathol 172: 156-166.
6. Hawkins PT, Eguinoa A, Qiu RG, Stokoe D, Cooke FT, Walters R et al. 1995. PDGF stimulates an increase in GTP-Rac via activation of phosphoinositide 3-kinase. Curr Biol 5: 393-403.
7. Higuchi M, Onishi K, Kikuchi C, Gotoh Y. (2008). Scaffolding function of PAK in the PDK1-Akt pathway. Nat Cell Biol 10: 1356-1364.
8. Hirsch E, Barberis L, Brancaccio M, Azzolino O, Xu D, Kyriakis JM et al. (2002). Defective Rac-mediated proliferation and survival after targeted mutation of the beta1 integrin cytodomain. J Cell Biol 157: 481-492.
9. Karlsson R, Pedersen ED, Wang Z, Brakebusch C. (2009). Rho GTPase function in tumorigenesis. Biochim Biophys Acta 1796: 91-98.
10. Keely PJ, Westwick JK, Whitehead IP, Der CJ, Parise LV. (1997). Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K. Nature 390: 632-636.
11. King AJ, Sun H, Diaz B, Barnard D, Miao W, Bagrodia S et al. (1998). The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338. Nature 396: 180-183.
12. Kissil JL, Walmsley MJ, Hanlon L, Haigis KM, Bender Kim CF, Sweet-Cordero A et al. (2007). Requirement for Rac1 in a K-ras induced lung cancer in the mouse. Cancer Res 67: 8089-8094.
13. Malliri A, van der Kammen RA, Clark K, van der Valk M, Michiels F, Collard JG. (2002). Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature 417: 867-871.
14. Maruta H, He H, Nheu T. (2002). Interfering with Ras signaling using membrane-permeable peptides or drugs. Methods Mol Biol 189: 75-85.
15. Mertens AE, Rygiel TP, Olivo C, van der Kammen R, Collard JG. (2005). The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex. J Cell Biol 170: 1029-1037.
16. Perez-Losada J, Balmain A. (2003). Stem-cell hierarchy in skin cancer. Nat Rev Cancer 3: 434-443.
17. Sahai E, Marshall CJ. (2002). RHO-GTPases and cancer. Nat Rev Cancer 2: 133-142.
18. Segrelles C, Ruiz S, Perez P, Murga C, Santos M, Budunova IV et al. (2002). Functional roles of Akt signaling in mouse skin tumorigen-esis. Oncogene 21: 53-64.
19. Skeen JE, Bhaskar PT, Chen CC, Chen WS, Peng XD, Nogueira V et al. (2006). Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent manner. Cancer Cell 10: 269-280.
20. Slack-Davis JK, Eblen ST, Zecevic M, Boerner SA, Tarcsafalvi A, Diaz HB et al. (2003). PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J Cell Biol 162: 281-291.
21. Sundberg-Smith LJ, Doherty JT, Mack CP, Taylor JM. (2005). Adhesion stimulates direct PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. J Biol Chem 280: 2055-2064.
22. Thomas EK, Cancelas JA, Chae HD, Cox AD, Keller PJ, Perrotti D et al. (2007). Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproli-ferative disease. Cancer Cell 12: 467-478.
23. Tscharntke M, Pofahl R, Chrostek-Grashoff A, Smyth N, Niessen C, Niemann C et al. (2007). Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1. J Cell Sci 120: 1480-1490.
24. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. (1995). Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326-1331.