A positive feedback loop involving EGFR/Akt/mTORC1 and IKK/NF-λB regulates head and neck squamous cell carcinoma proliferation

Oncotarget

Volumn 7, Issue 22, 2016, Pages 31892-31906

  Li, Zhipeng ^a   Yang, Zejia ^a   Passaniti, Antonino ^a   Lapidus, Rena G ^a   Liu, Xuefeng ^b   Cullen, Kevin J ^a   Dan, Han C ^a  

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

^b GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Akt; Head and neck cancer; IKK; mTOR; NF kappaB

Indexed keywords

CASPASE; CISPLATIN; CMPDA; EPIDERMAL GROWTH FACTOR RECEPTOR; I KAPPA B KINASE BETA; I KAPPA B KINASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RAPAMYCIN; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; EGFR PROTEIN, HUMAN; I KAPPA B KINASE; IKBKB PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR;

APOPTOSIS; ARTICLE; CANCER GROWTH; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; IC50; POSITIVE FEEDBACK; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA CELL LINE; UPREGULATION; ANTAGONISTS AND INHIBITORS; DOSE RESPONSE; DRUG EFFECTS; DRUG RESISTANCE; ENZYMOLOGY; GENETIC TRANSFECTION; GENETICS; HEAD AND NECK TUMOR; METABOLISM; PATHOLOGY; PHYSIOLOGICAL FEEDBACK; RNA INTERFERENCE; SQUAMOUS CELL CARCINOMA; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; CELL PROLIFERATION; CISPLATIN; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, NEOPLASM; FEEDBACK, PHYSIOLOGICAL; HEAD AND NECK NEOPLASMS; HUMANS; I-KAPPA B KINASE; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; NF-KAPPA B; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, EPIDERMAL GROWTH FACTOR; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TRANSFECTION;

EID: 84973520321     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.7441     Document Type: Article

References (58)

1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007; 57:43-66.
2. Freudlsperger C, Burnett JR, Friedman JA, Kannabiran VR, Chen Z, Van Waes C. EGFR-PI3K-AKT-mTOR Signaling in Head and Neck Squamous Cell Carcinomas-Attractive Targets for Molecular-Oriented Therapy. Expert Opin Ther Targets. 2011; 15:63-74.
3. Park BJ, Chiosea SI, Grandis JR. Molecular changes in the multistage pathogenesis of head and neck cancer. Cancer Biomark. 2010; 9:325-339.
4. Ha PK, Chang SS, Glazer CA, Califano JA, Sidransky D. Molecular techniques and genetic alterations in head and neck cancer. Oral Oncol. 2009; 45:335-339.
5. Sharafinski ME, Ferris RL, Ferrone S, Grandis JR. Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck. Head Neck. 2010; 32: 1412-1421.
6. Kalyankrishna S, Grandis JR. Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol. 2006; 24:2666-2672.
7. Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res. 1993; 53:3579-3584.
8. Bei R, Budillon A, Masuelli L, Cereda V, Vitolo D, Di Gennaro E, Ripavecchia V, Palumbo C, Ionna F, Losito S, Modesti A, Kraus MH, Muraro R. Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients. J Pathol. 2004; 204:317-325.
9. Ongkeko WM, Altuna X, Weisman RA, Wang-Rodriguez J. Expression of protein tyrosine kinases in head and neck squamous cell carcinomas. Am J Clin Pathol. 2005; 124:71-76.
10. Wang F, Arun P, Friedman J, Chen Z, Van Waes C. Current and potential inflammation targeted therapies in head and neck cancer. Curr Opin Pharmacol. 2009; 9:389-395.
11. Brown M, Cohen J, Arun P, Chen Z, Van Waes C. NF-kappaB in carcinoma therapy and prevention. Expert Opin Ther Targets. 2008; 12:1109-1122.
12. Nguyen SA, Walker D, Gillespie MB, Gutkind JS, Day TA. mTOR inhibitors and its role in the treatment of head and neck squamous cell carcinoma. Curr Treat Options Oncol. 2012; 13:71-81.
13. Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002; 296: 1655-1657.
14. Wong KK, Engelman JA, Cantley LC. Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev. 2010; 20:87-90.
15. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007; 129: 1261-1274.
16. Kim D, Dan HC, Park S, Yang L, Liu Q, Kaneko S, Ning J, He L, Yang H, Sun M, Nicosia SV, Cheng JQ. AKT/PKB signaling mechanisms in cancer and chemoresistance. Front Biosci. 2005; 10:975-987.
17. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 2002; 110:163-175.
18. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002; 110:177-189.
19. Lamming DW, Sabatini DM. A Central role for mTOR in lipid homeostasis. Cell Metab. 2013; 18:465-469.
20. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012; 149:274-293.
21. Inoki K, Li Y, Zhu T, Wu J, Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signaling. Nat Cell Biol. 2002; 4:648-657.
22. Gao X, Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung RS, Ru B, Pan D. Tsc tumour suppressor proteins antagonize amino-acid-TOR signaling. Nat Cell Biol. 2002; 4:699-704.
23. Jaeschke A, Hartkamp J, Saitoh M, Roworth W, Nobukuni T, Hodges A, Sampson J, Thomas G, Lamb R. Tuberous sclerosis complex tumor suppressor-mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent. J Cell Biol. 2002; 159:217-224.
24. Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci USA. 2002; 99:13571-13576.
25. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. Rictor, a novel binding partner of mTOR, defines a rapamycininsensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004; 14:1296-1302.
26. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictormTOR complex. Science. 2005; 307:1098-1101.
27. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, Brown M, Fitzgerald KJ, Sabatini DM. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006; 11:859-871.
28. Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004; 18:2195-224.
29. Bassères DS, Baldwin AS. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene. 2006; 25:6817-6830.
30. Baldwin AS. Regulation of cell death and autophagy by IKK and NF-?B: critical mechanisms in immune function and cancer. Immunol Rev. 2012; 246:327-345.
31. Bonizzi G, Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004; 25:280-288.
32. Claus Scheidereit. IkappaB kinase complexes: gateways to NF-kappaB activation and transcription. Oncogene. 2006; 25:6685-6705.
33. Dan HC, Adli M, Baldwin AS. Regulation of mammalian target of rapamycin activity in PTEN-inactive prostate cancer cells by I kappa B kinase alpha. Cancer Res. 2007; 67: 6263-6269.
34. Dan HC, Cooper MJ, Cogswell PC, Duncan JA, Ting JP, Baldwin AS. Akt-dependent regulation of NF-(kappa) B is controlled by mTOR and Raptor in association with IKK. Genes Dev. 2008; 22:1490-1500.
35. Gioanni J, Fischel JL, Lambert JC, Demard F, Mazeau C, Zanghellini E, Ettore F, Formento P, Chauvel P, Lalanne CM, Courdi A. Two new human tumor cell lines derived from squamous cell carcinomas of the tongue: establishment, characterization and response to cytotoxic treatment. Eur J Cancer Clin Oncol. 1988; 24:1445-1455.
36. Sakurai H, Chiba H, Miyoshi H, Sugita T, Toriumi W. IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain. J Biol Chem. 1999; 274:30353-30356.
37. Yang F, Tang E, Guan K, Wang CY. IKK beta plays an essential role in the phosphorylation of RelA/ p65 on serine 536 induced by lipopolysaccharide. J Immunol. 2003; 170:5630-5635.
38. Sakurai H, Suzuki S, Kawasaki N, Nakano H, Okazaki T, Chino A, Doi T, Saiki I. Tumor necrosis factor-alpha-induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway. J Biol Chem. 2003; 278:36916-36923.
39. Takada Y, Singh S, Aggarwal BB. Identification of a p65 peptide that selectively inhibits NF-kappa B activation induced by various inflammatory stimuli and its role in down-regulation of NF-kappaB-mediated gene expression and up-regulation of apoptosis. J Biol Chem. 2004; 279:15096-15104.
40. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006; 66:1500-1508.
41. Manning BD. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol. 2004; 167:399-403.
42. Kelsey I, Manning BD. mTORC1 status dictates tumor response to targeted therapeutics. Sci Signal. 2013; 6: pe31.
43. Gills JJ, Dennis PA. Perifosine: update on a novel Akt inhibitor. Curr Oncol Rep. 2009; 11:102-110.
44. Nottingham LK, Yan CH, Yang X, Si H, Coupar J, Bian Y, Cheng TF, Allen C, Arun P, Gius D, Dang L, Van Waes C, Chen Z. Aberrant IKKa and IKKß cooperatively activate NF-?B and induce EGFR/AP1 signaling to promote survival and migration of head and neck cancer. Oncogene. 2014; 33:1135-1147.
45. Ziegelbauer K, Gantner F, Lukacs NW, Berlin A, Fuchikami K, Niki T, Sakai K, Inbe H, Takeshita K, Ishimori M, Komura H, Murata T, Lowinger T, et al. A selective novel low-molecular-weight inhibitor of IkappaB kinase-beta (IKK-beta) prevents pulmonary inflammation and shows broad anti-inflammatory activity. Br J Pharmacol. 2005; 145:178-192.
46. Duncan EA, Goetz CA, Stein SJ, Mayo KJ, Skaggs BJ, Ziegelbauer K, Sawyers CL, Baldwin AS. IkappaB kinase beta inhibition induces cell death in Imatinibresistant and T315I Dasatinib-resistant BCR-ABL+ cells. Mol Cancer Ther. 2008; 7:391-397.
47. Bednarski BK, Ding X, Coombe K, Baldwin AS, Kim HJ. Active roles for inhibitory kappaB kinases alpha and beta in nuclear factor-kappaB-mediated chemoresistance to doxorubicin. Mol Cancer Ther. 2008; 7:1827-1835.
48. Bassères DS, Ebbs A, Cogswell PC, Baldwin AS. IKK is a therapeutic target in KRAS-Induced lung cancer with disrupted p53 activity. Genes Cancer. 2014; 5:41-55.
49. Pendleton KP, Grandis JR. Cisplatin-Based Chemotherapy Options for Recurrent and/or Metastatic Squamous Cell Cancer of the Head and Neck. Clin Med Insights Ther. 2013; 2013: doi: 10.4137/CMT.S10409.
50. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular mechanisms of cisplatin resistance. Oncogene. 2012; 31:1869-1883.
51. Rabik CA, Dolan ME. Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 2007; 33:9-23.
52. Bhave SL, Teknos TN, Pan Q. Molecular parameters of head and neck cancer metastasis. Crit Rev Eukaryot Gene Expr. 2011; 21:143-153.
53. Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB. NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase.Nature. 1999; 401:82-85.
54. Yuan ZQ, Feldman RI, Sussman GE, Coppola D, Nicosia SV, Cheng JQ. AKT2 inhibition of cisplatin-induced JNK/ p38 and Bax activation by phosphorylation of ASK1: implication of AKT2 in chemoresistance. J Biol Chem. 2003; 278:23432-23440.
55. Wang CY, Cusack JC Jr, Liu R, Baldwin AS. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med. 1999; 5:412-417.
56. Kim SG, Veena MS, Basak SK, Han E, Tajima T, Gjertson DW, Starr J, Eidelman O, Pollard HB, Srivastava M, Srivatsan ES, Wang MB. Curcumin treatment suppresses IKKß kinase activity of salivary cells of patients with head and neck cancer: a pilot study. Clin Cancer Res. 2011; 17:5953-5961.
57. Duarte VM, Han E, Veena MS, Salvado A, Suh JD, Liang LJ, Faull KF, Srivatsan ES, Wang MB. Curcumin enhances the effect of cisplatin in suppression of head and neck squamous cell carcinoma via inhibition of IKKß protein of the NF?B pathway. Mol Cancer Ther. 2010; 9:2665-2675.
58. Aggarwal S, Takada Y, Singh S, Myers JN, Aggarwal BB. Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-kappaB signaling. Int J Cancer. 2004; 111:679-692.