Overexpression of PIK3CA in murine head and neck epithelium drives tumor invasion and metastasis through PDK1 and enhanced TGFβ signaling

Oncogene

Volumn 35, Issue 35, 2016, Pages 4641-4652

  Du, L ^a,b   Chen, X ^a   Cao, Y ^a,b   Lu, L ^a   Zhang, F ^a   Bornstein, S ^c   Li, Y ^c   Owens, P ^c   Malkoski, S ^a   Said, S ^a   Jin, F ^b   Kulesz Martin, M ^c   Gross, N ^c   Wang, X J ^a   Lu, S L ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b CHINA MEDICAL UNIVERSITY   (China)

^c OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 NITROQUINOLINE 1 OXIDE; ASPARTIC ACID; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR4; CYCLIN D1; CYTOKERATIN 1; CYTOKERATIN 5; GALUNISERTIB; GLUTAMIC ACID; K RAS PROTEIN; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MESSENGER RNA; MIFEPRISTONE; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PIK3CA PROTEIN; PROTEIN; PROTEIN P16; STAT3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UVOMORULIN; VIMENTIN; PHOSPHATIDYLINOSITOL 3 KINASE; PIK3CA PROTEIN, MOUSE; PROTEIN SERINE THREONINE KINASE; PYRUVATE DEHYDROGENASE (ACETYL-TRANSFERRING) KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER SUSCEPTIBILITY; CARCINOMA IN SITU; CELL MIGRATION; CELL PROLIFERATION; COMPARATIVE STUDY; CONTROLLED STUDY; EPITHELIUM HYPERPLASIA; GENETIC SUSCEPTIBILITY; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; LIGAND BINDING; METASTASIS; MOUSE; NONHUMAN; NUTRITIONAL STATUS; POINT MUTATION; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR GROWTH; TUMOR INVASION; UPREGULATION; WESTERN BLOTTING; ANIMAL; BIOSYNTHESIS; CANCER STEM CELL; CELL TRANSFORMATION; DISEASE MODEL; EPITHELIAL MESENCHYMAL TRANSITION; EPITHELIUM; FEMALE; GENE EXPRESSION REGULATION; GENETICS; HEAD AND NECK TUMOR; LYMPH NODE METASTASIS; MALE; MUTATION; PATHOLOGY; SIGNAL TRANSDUCTION; TRANSGENIC ANIMAL;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; DISEASE MODELS, ANIMAL; EPITHELIAL-MESENCHYMAL TRANSITION; EPITHELIUM; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HEAD AND NECK NEOPLASMS; HUMANS; LYMPHATIC METASTASIS; MALE; MICE; MUTATION; NEOPLASM INVASIVENESS; NEOPLASTIC STEM CELLS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 84958260754     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2016.1     Document Type: Article

References (54)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90
2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63: 11-30
3. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer 2011; 11: 9-22
4. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006; 7: 606-619
5. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 2009; 8: 627-644
6. Du L, Shen J, Weems A, Lu SL. Role of phosphatidylinositol-3-kinase pathway in head and neck squamous cell carcinoma. J Oncol 2012; 2012: 450179
7. Vogt PK, Gymnopoulos M, Hart JR. PI 3-kinase and cancer: changing accents. Curr Opin Genet Dev 2009; 19: 12-17
8. Vasudevan KM, Barbie DA, Davies MA, Rabinovsky R, McNear CJ, Kim JJ, et al. AKTindependent signaling downstream of oncogenic PIK3CA mutations in human cancer. Cancer Cell 2009; 16: 21-32
9. Marsh Durban V, Deuker MM, Bosenberg MW, Phillips W, McMahon M. Differential AKT dependency displayed by mouse models of BRAFV600E-initiated melanoma. J Clin Invest 2013; 123: 5104-5118
10. Lui VW, Hedberg ML, Li H, Vangara BS, Pendleton K, Zeng Y, et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov 2013; 3: 761-769
11. Pickering CR, Zhang J, Yoo SY, Bengtsson L, Moorthy S, Neskey DM, et al. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 2013; 3: 770-781
12. Iglesias-Bartolome R, Martin D, Gutkind JS. Exploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets. Cancer Discov 2013; 3: 722-725
13. Morris LG, Taylor BS, Bivona TG, Gong Y, Eng S, Brennan CW, et al. Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers. Proc Natl Acad Sci U S A 2011; 108: 19024-19029
14. Woenckhaus J, Steger K, Werner E, Fenic I, Gamerdinger U, Dreyer T, et al. Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma. J Pathol 2002; 198: 335-342
15. Kozaki K, Imoto I, Pimkhaokham A, Hasegawa S, Tsuda H, Omura K, et al. PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. Cancer Sci 2006; 97: 1351-1358
16. Estilo CL, O-Charoenrat P, Ngai I, Patel SG, Reddy PG, Dao S, et al. The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110alpha in squamous cell carcinoma of the oral tongue. Clin Cancer Res 2003; 9: 2300-2306
17. Fenic I, Steger K, Gruber C, Arens C, Woenckhaus J. Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell carcinoma. Oncol Rep 2007; 18: 253-259
18. Lu SL, Reh D, Li AG, Woods J, Corless CL, Kulesz-Martin M, et al. Overexpression of transforming growth factor beta1 in head and neck epithelia results in inflammation, angiogenesis, and epithelial hyperproliferation. Cancer Res 2004; 64: 4405-4410
19. Vitale-Cross L, Czerninski R, Amornphimoltham P, Patel V, Molinolo AA, Gutkind JS. Chemical carcinogenesis models for evaluating molecular-Targeted prevention and treatment of oral cancer. Cancer Prev Res (Phila) 2009; 2: 419-422
20. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelialmesenchymal transition generates cells with properties of stem cells. Cell 2008; 133: 704-715
21. Iliopoulos D, Polytarchou C, Hatziapostolou M, Kottakis F, Maroulakou IG, Struhl K, et al. MicroRNAs differentially regulated by Akt isoforms control EMT and stem cell renewal in cancer cells. Sci Signal 2009; 2: ra62
22. Marvel D, Gabrilovich DI. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest 2015; 125: 3356-3364
23. Lu SL, Herrington H, Reh D, Weber S, Bornstein S, Wang D, et al. Loss of transforming growth factor-beta type II receptor promotes metastatic head-And-neck squamous cell carcinoma. Genes Dev 2006; 20: 1331-1342
24. Bornstein S, White R, Malkoski S, Oka M, Han G, Cleaver T, et al. Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation. J Clin Invest 2009; 119: 3408-3419
25. Liu P, Cheng H, Santiago S, Raeder M, Zhang F, Isabella A, et al. Oncogenic PIK3CAdriven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms. Nat Med 2011; 17: 1116-1120
26. Klarenbeek S, van Miltenburg MH, Jonkers J. Genetically engineered mouse models of PI3K signaling in breast cancer. Mol Oncol 2013; 7: 146-164
27. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008; 14: 1351-1356
28. Kinross KM, Montgomery KG, Kleinschmidt M, Waring P, Ivetac I, Tikoo A, et al. An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice. J Clin Invest 2012; 122: 553-557
29. Hare LM, Phesse TJ, Waring PM, Montgomery KG, Kinross KM, Mills K, et al. Physiological expression of the PI3K-Activating mutation Pik3ca(H1047R) combines with Apc loss to promote development of invasive intestinal adenocarcinomas in mice. Biochem J 2014; 458: 251-258
30. Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, Gilcrease MZ, Krishnamurthy S, Lee JS, et al. Characterization of a naturally occurring breast cancer subset enriched in epithelial-To-mesenchymal transition and stem cell characteristics. Cancer Res 2009; 69: 4116-4124
31. Wallin JJ, Guan J, Edgar KA, Zhou W, Francis R, Torres AC, et al. Active PI3K pathway causes an invasive phenotype which can be reversed or promoted by blocking the pathway at divergent nodes. PLoS One 2012; 7: e36402
32. Fan QW, Cheng C, Knight ZA, Haas-Kogan D, Stokoe D, James CD, et al. EGFR signals to mTOR through PKC and independently of Akt in glioma. Sci Signal 2009; 2: ra4
33. Lauring J, Cosgrove DP, Fontana S, Gustin JP, Konishi H, Abukhdeir AM, et al. Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations. Oncogene 2010; 29: 2337-2345
34. Xue G, Restuccia DF, Lan Q, Hynx D, Dirnhofer S, Hess D, et al. Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-Talk between PI3K/Akt and TGF-beta signaling axes. Cancer Discov 2012; 2: 248-259
35. Curry NL, Mino-Kenudson M, Oliver TG, Yilmaz OH, Yilmaz VO, Moon JY, et al. Ptennull tumors cohabiting the same lung display differential AKT activation and sensitivity to dietary restriction. Cancer Discov 2013; 3: 908-921
36. Wong KK. Oral-specific chemical carcinogenesis in mice: an exciting model for cancer prevention and therapy. Cancer Prev Res (Phila) 2009; 2: 10-13
37. Weber SM, Bornstein S, Li Y, Malkoski SP, Wang D, Rustgi AK, et al. Tobacco-specific carcinogen nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induces AKT activation in head and neck epithelia. Int J Oncol 2011; 39: 1193-1198
38. Moral M, Segrelles C, Lara MF, Martínez-Cruz AB, Lorz C, Santos M, et al. Akt activation synergizes with Trp53 loss in oral epithelium to produce a novel mouse model for head and neck squamous cell carcinoma. Cancer Res 2009; 69: 1099-1108
39. Pearce LR, Komander D, Alessi DR. The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol 2010; 11: 9-22
40. Finlay DK, Sinclair LV, Feijoo C, Waugh CM, Hagenbeek TJ, Spits H, et al. Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes. J Exp Med 2009; 206: 2441-2454
41. Feng Q, Di R, Tao F, Chang Z, Lu S, Fan W, et al. PDK1 regulates vascular remodeling and promotes epithelial-mesenchymal transition in cardiac development. Mol Cell Biol 2010; 30: 3711-3721
42. Maurer M, Su T, Saal LH, Koujak S, Hopkins BD, Barkley CR, et al. 3-Phosphoinositidedependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma. Cancer Res 2009; 69: 6299-6306
43. Garcia-Carracedo D, Turk AT, Fine SA, Akhavan N, Tweel BC, Parsons R, et al. Loss of PTEN expression is associated with poor prognosis in patients with intraductal papillary mucinous neoplasms of the pancreas. Clin Cancer Res 2013; 19: 6830-6841
44. Scortegagna M, Ruller C, Feng Y, Lazova R, Kluger H, Li JL, et al. Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of Braf: : Pten melanoma. Oncogene 2013; 33: 4330-4339
45. Eser S, Reiff N, Messer M, Seidler B, Gottschalk K, Dobler M, et al. Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer. Cancer Cell 2013; 23: 406-420
46. Bhola NE, Freilino ML, Joyce SC, Sen M, Thomas SM, Sahu A, et al. Antitumor mechanisms of targeting the PDK1 pathway in head and neck cancer. Mol Cancer Ther 2012; 11: 1236-1246
47. Raimondi C, Chikh A, Wheeler AP, Maffucci T, Falasca M. A novel regulatory mechanism links PLCgamma1 to PDK1. J Cell Sci 2012; 125: 3153-3163
48. Tan J, Li Z, Lee PL, Guan P, Aau MY, Lee ST, et al. PDK1 signaling toward PLK1-MYC activation confers oncogenic transformation, tumor-initiating cell activation, and resistance to mTOR-Targeted therapy. Cancer Discov 2013; 3: 1156-1171
49. Zhang L, Zhou F, ten Dijke P. Signaling interplay between transforming growth factorbeta receptor and PI3K/AKT pathways in cancer. Trends Biochem Sci 2013; 38: 612-620
50. Yi JY, Shin I, Arteaga CL. Type I transforming growth factor beta receptor binds to and activates phosphatidylinositol 3-kinase. J Biol Chem 2005; 280: 10870-10876
51. Du Y, Peyser ND, Grandis JR. Integration of molecular targeted therapy with radiation in head and neck cancer. Pharmacol Ther 2014; 142: 88-98
52. Signore M, Pelacchi F, di Martino S, Runci D, Biffoni M, Giannetti S, et al. Combined PDK1 and CHK1 inhibition is required to kill glioblastoma stem-like cells in vitro and in vivo. Cell Death Dis 2014; 5: e1223
53. Akhurst RJ, Hata A. Targeting the TGFbeta signalling pathway in disease. Nat Rev Drug Discov 2012; 11: 790-811
54. Han G, Lu SL, Li AG, He W, Corless CL, Kulesz-Martin M, et al. Distinct mechanisms of TGF-beta1-mediated epithelial-To-mesenchymal transition and metastasis during skin carcinogenesis. J Clin Invest 2005; 115: 1714-1723