期刊论文详细信息
Cancer Cell International
Activation of EGFR-PI3K-AKT signaling is required for Mycoplasma hyorhinis-promoted gastric cancer cell migration
Chengchao Shou1  Like Qu1  Hongying Duan1 
[1] Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Beijing 100142, China
关键词: EGFR;    PI3K-AKT;    p37;    Gastric cancer;    Mycoplasma hyorhinis;   
Others  :  1121614
DOI  :  10.1186/s12935-014-0135-3
 received in 2014-06-23, accepted in 2014-11-20,  发布年份 2014
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【 摘 要 】

Persistent infection of Mycoplasma hyorhinis (M. hyorhinis) was associated with gastric cancer cell migration and invasion, but the mechanisms were not well understood. Herein, we found that M. hyorhinis activated phosphoinositide 3-kinase (PI3K)-AKT signaling axis in gastric cancer cell lines. Epidermal growth factor receptor (EGFR) was upstream of PI3K-AKT signaling in the context of M. hyorhinis infection, because phosphorylation of AKT Serine 473 was almost completely attenuated by the EGFR inhibitor AG1478 or by EGFR knockdown. Phosphorylation of AKT S473 induced by M. hyorhinis infection was also abolished by PI3K inhibitor wortmannin. Furthermore, we found that p37, a membrane protein of M. hyorhinis, could also promote M. hyorhinis-induced PI3K-AKT signaling activation and cell migration. In addition, pre-treatment with AG1478 or wortmannin significantly inhibited cell migration induced by M. hyorhinis infection or p37 treatment. In conclusion, EGFR-PI3K-AKT signaling plays an important role in M. hyorhinis-promoted cell migration in gastric cancer cells, thus providing a clue to the pathogenesis of M. hyorhinis in gastric cancer.

【 授权许可】

   
2014 Duan et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2008, 2010(127):2893-2917.
  • [2]Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ: Helicobacter pylori infection and gastric carcinoma in a population of Japanese Americans in Hawaii. N Engl J Med 1991, 325:1132-1136.
  • [3]Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999, 189:12-19.
  • [4]Paton GR, Jacobs JP, Perkins FT: Chromosome changes in human diploid-cell cultures infected with Mycoplasma. Nature 1965, 207:43-45.
  • [5]Chan PJ, Seraj IM, Kalugdan TH, King A: Prevalence of mycoplasma conserved DNA in malignant ovarian cancer detected using sensitive PCR-ELISA. Gynecol Oncol 1996, 63:258-260.
  • [6]Kidder M, Chan PJ, Seraj IM, Patton WC, King A: Assessment of archived paraffin-embedded cervical condyloma tissues for mycoplasma-conserved DNA using sensitive PCR-ELISA. Gynecol Oncol 1998, 71:254-257.
  • [7]Barykova YA, Logunov DY, Shmarov MM, Vinarov AZ, Fiev DN, Vinarova NA, Rakovskaya IV, Baker PS, Shyshynova I, Stephenson AJ: Association of Mycoplasma hominis infection with prostate cancer. Oncotarget 2011, 2:289-297.
  • [8]Huang S, Li JY, Wu J, Meng L, Shou CC: Mycoplasma infections and different human carcinomas. World J Gastroenterol 2001, 7:266-269.
  • [9]Namiki K, Goodison S, Porvasnik S, Allan RW, Iczkowski KA, Urbanek C, Reyes L, Sakamoto N, Rosser CJ: Persistent exposure to mycoplasma induces malignant transformation of human prostate cells. PLoS One 2009, 4:e6872.
  • [10]Yang H, Qu L, Ma H, Chen L, Liu W, Liu C, Meng L, Wu J, Shou C: Mycoplasma hyorhinis infection in gastric carcinoma and its effects on the malignant phenotypes of gastric cancer cells. BMC Gastroenterol 2010, 10:132. BioMed Central Full Text
  • [11]Urbanek C, Goodison S, Chang M, Porvasnik S, Sakamoto N, Li CZ, Boehlein SK, Rosser CJ: Detection of antibodies directed at M hyorhinis p37 in the serum of men with newly diagnosed prostate cancer. BMC Cancer 2011, 11:233. BioMed Central Full Text
  • [12]Sippel KH, Robbins AH, Reutzel R, Boehlein SK, Namiki K, Goodison S, Agbandje-McKenna M, Rosser CJ, McKenna R: Structural insights into the extracytoplasmic thiamine-binding lipoprotein p37 of Mycoplasma hyorhinis. J Bacteriol 2009, 191:2585-2592.
  • [13]Gong M, Meng L, Jiang B, Zhang J, Yang H, Wu J, Shou C: p37 from Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis through activation of MMP-2 and followed by phosphorylation of EGFR. Mol Cancer Ther 2008, 7:530-537.
  • [14]Le XF, Merchant O, Bast RC, Calin GA: The roles of MicroRNAs in the cancer invasion-metastasis cascade. Cancer Microenviron 2010, 3:137-147.
  • [15]Weigelt B, Peterse JL, van‘t Veer LJ: Breast cancer metastasis: markers and models. Nat Rev Cancer 2005, 5:591-602.
  • [16]Biancoa R, Melisia D, Ciardiellob F, Tortoraa G: Key cancer cell signal transduction pathways as therapeutic targets. Eur J Cancer 2006, 42:290-294.
  • [17]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.
  • [18]Dummler B, Hemmings BA: Physiological roles of PKB/Akt isoforms in development and disease. Biochem Soc Trans 2007, 35:231-235.
  • [19]Fayard E, Xue G, Parcellier A, Bozulic L, Hemmings BA: Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway. Curr Top Microbiol Immunol 2010, 346:31-56.
  • [20]Xue G, Hemmings BA: PKB/Akt-dependent regulation of cell motility. J Natl Cancer Inst 2013, 105:393-404.
  • [21]Shukla S, MacLennan GT, Hartman DJ, Fu P, Resnick MI, Gupta S: Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int J Cancer 2007, 121:1424-1432.
  • [22]O’Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL: mTOR Inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006, 66:1500-1508.
  • [23]Keates S, Keates AC, Katchar K, Peek RM Jr, Kelly CP: Helicobacter pylori induces up-regulation of the epidermal growth factor receptor in AGS gastric epithelial cells. J Infect Dis 2007, 196:95-103.
  • [24]Tabassam FH, Graham DY, Yamaoka Y: Helicobacter pylori activate epidermal growth factor receptor- and phosphatidylinositol 3-OH kinase-dependent Akt and glycogen synthase kinase 3β phosphorylation. Cell Microbiol 2009, 11:70-82.
  • [25]Pehlivan M, Itirli G, Onay H, Bulut H, Koyuncuoglu M, Pehlivan S: Does Mycoplasma sp. play role in small cell lung cancer? Lung Cancer 2004, 45:129-130.
  • [26]Hrbacek J, Urban M, Hamsikova E, Tachezy R, Eis V, Brabec M, Heracek J: Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients: a case–control study. BMC Cancer 2011, 11:53. BioMed Central Full Text
  • [27]Dong ZW, Wan WH, Li ZP, Qiu WR, Wei SM: A monoclonal antibodies PD4 against gastric cancer cell line MGC803. Shengwu Huaxue Zazhi 1985, 1:52-58.
  • [28]Ning JY, Sun GX, Huang S, Ma H, An P, Meng L, Song SM, Wu J, Shou CC: Identification of antigens by monoclonal antibody PD4 and its expression in Escherichia coli. World J Gastroenterol 2003, 9:2164-2168.
  • [29]Engelman JA, Zejnullahu K, Mitsudomi T, Hyland C, Oh Park J, Lindeman N, Gale CM, Zhao X, Christensen J, Rogers RM: Mechanisms of activating PI3K signaling in lung cancers that become resistant EGFR tyrosine kinase inhibitors: D2-07. J Thorac Oncol 2007, 2:396.
  • [30]Courtney KD, Corcoran RB, Engelman JA: The PI3K Pathway As Drug Target in Human Cancer. J Clin Oncol 2010, 28:1075-1083.
  • [31]Chen YT, Tan KA, Pang LY, Argyle DJ: The class I PI3K/Akt pathway is critical for cancer cell survival in dogs and offers an opportunity for therapeutic intervention. BMC Vet Res 2012, 8:73. BioMed Central Full Text
  • [32]Sakr RA, Weigelt B, Chandarlapaty S, Andrade VP, Guerini-Rocco E, Giri D, Ng CK, Cowell CF, Rosen N, Reis-Filho JS: PI3K pathway activation in high-grade ductal carcinoma in situ-implications for progression to invasive breast carcinoma. Clin Cancer Res 2014, 20:2326-2337.
  • [33]Rexer BN, Chanthaphaychith S, Dahlman KB, Arteaga CL: Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells. Breast Cancer Res 2014, 16:R9. BioMed Central Full Text
  • [34]Toker A, Yoeli-Lerner M: Akt signaling and cancer: surviving but not moving on. Cancer Res 2006, 66:3963-3966.
  • [35]Schlieman MG, Fahy BN, Ramsamooj R, Beckett L, Bold RJ: Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br J Cancer 2003, 89:2110-2115.
  • [36]Altomare DA, Wang HQ, Skele KL, De Rienzo A, Klein-Szanto AJ, Godwin AK, Testa JR: AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth. Oncogene 2004, 23:5853-5857.
  • [37]Lin HJ, Hsieh FC, Song H, Lin J: Elevated phosphorylation and activation of PDK-1/AKT pathway in human breast cancer. Br J Cancer 2005, 93:1372-1381.
  • [38]Sarker D, Reid AH, Yap TA, De Bono JS: Targeting the PI3K/AKT pathway for the treatment of prostate cancer. Clin Cancer Res 2009, 15:4799-4805.
  • [39]Kumar A, Rajendran V, Sethumadhavan R, Purohit R: AKT kinase pathway: a leading target in cancer research. Cancer Cell 2003, 4:257-262.
  • [40]Song G, Ouyang G, Bao S: The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 2005, 9:59-71.
  • [41]Yap TA, Garrett MD, Walton MI, Raynaud F, De Bono JS, Workman P: Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol 2008, 8:393-412.
  • [42]Onishi K, Higuchi M, Asakura T, Masuyama N, Gotoh Y: The PI3K-Akt pathway promotes microtubule stabilization in migrating fibroblasts. Genes Cells 2007, 12:535-546.
  • [43]Yadav V, Denning MF: Fyn is induced by Ras/PI3K/Akt signaling and is required for enhanced invasion/migration. Mol Carcinog 2011, 50:346-352.
  • [44]Folgiero V, Bachelder RE, Bon G, Sacchi A, Falcioni R, Mercurio AM: The alpha6beta4 integrin can regulate ErbB-3 expression: implications for alpha6beta4 signaling and function. Cancer Res 2007, 67:1645-1652.
  • [45]Park BK, Zeng X, Glazer RI: Akt1 induces extracellular matrix invasion and matrix metalloproteinase-2 activity in mouse mammary epithelial cells. Cancer Res 2001, 61:7647-7653.
  • [46]Enomoto A, Murakami H, Asai N, Morone N, Watanabe T, Kawai K, Murakumo Y, Usukura J, Kaibuchi K, Takahashi M: Akt/PKB regulates actin organization and cell motility via Girdin/APE. Dev Cell 2009, 9:389-402.
  • [47]Kim D, Kim S, Koh H, Yoon SO, Chung AS, Cho KS, Chung J: Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J 2001, 15:1953-1962.
  • [48]Tanno S, Mitsuuchi Y, Altomare DA, Xiao GH, Testa JR: AKT activation up-regulates insulin-like growth factor receptor expression and promotes invasiveness of human pancreatic cancer cells. Cancer Res 2001, 61:589-593.
  • [49]Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, Van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN, Larue L: The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 2003, 63:2172-2178.
  • [50]Vivanco I, Sawyers CL: The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002, 2:489-501.
  • [51]Luo C, Wu Q, Huang XN, Sun AS, Shi JS: Ginkgo biloba leaf extract enhances levels of caspase-3 and amyloid precursor protein in normal rat hippocampus. Acta Pharmacol Sin 2003, 24:152-156.
  • [52]Hayflick L, Stinebring WR: Intracellular growth of pleura pneumonia like organisms (PPLO) in tissue culture and in ovo. Ann N Y Acad Sci 1960, 79:433-449.
  • [53]Taylor G, Taylor-Robinson D, Slavin G: Effect of immunosuppression on arthritis in mice induced by Mycoplasma pulmonis. Ann Rheum Dis 1974, 33:376.
  • [54]Caron J, Ouardani M, Dea S: Diagnosis and differentiation of Mycoplasma hyopneumoniae and Mycoplasma hyorhinis infections in pigs by PCR amplification of the p36 and p46 genes. J Clin Microbiol 2000, 38:1390-1396.
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