DOI QR코드

DOI QR Code

Effect of STAT3 on Lysophosphatidic Acid-Induced Oral Cancer Cell Invasion

  • Song, Zi Hae (Department of Pharmacology, College of Medicine, Konyang University) ;
  • Cho, Kyung Hwa (Department of Pharmacology, College of Medicine, Konyang University) ;
  • Kim, Jin Young (Department of Pharmacology, College of Medicine, Konyang University) ;
  • Lee, Hoi Young (Department of Pharmacology, College of Medicine, Konyang University)
  • 투고 : 2019.05.07
  • 심사 : 2019.05.27
  • 발행 : 2019.06.30

초록

Background: Oral cancer has a high incidence worldwide and has been closely associated with smoking, alcohol, and infection by the human papillomavirus. Metastasis is highly important for oral cancer survival. Lysophosphatidic acid (LPA) is a bioactive lipid mediator that promotes various cellular processes, including cell survival, proliferation, metastasis, and invasion. Signal transducer and activator of transcription (STATs) are transcription factors that mediate gene expression. Among the seven types of STATs in mammals, STAT3 is involved in invasion and metastasis of numerous tumors. However, little is known about the role of STAT3 in oral tumor invasion. In the present study, we hypothesized that STAT3 mediates LPA-induced oral cancer invasion. Methods: Immunoblotting was performed to analyze LPA-induced STAT3 activation. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed to assess the survival rates of YD-10B cells. STAT3 levels in LPA-treated oral tumor cells were evaluated by performing in vitro invasion assay. Results: To the best of our knowledge, this is the first study to demonstrate that LPA enhances STAT3 phosphorylation in oral cancer. In addition, treatment with WP1066, a selective inhibitor of STAT3, at a concentration that does not cause severe reduction in cell viability, significantly attenuated LPA-induced YD-10B cancer cell invasion. Conclusion: The results suggested that LPA induces oral tumor cells with greater invasive potential via STAT3 activation. Our findings provided important insights into the mechanisms underlying mouth neoplasms.

키워드

참고문헌

  1. Xie C, Ji N, Tang Z, Li J, Chen Q: The role of extracellular vesicles from different origin in the microenvironment of head and neck cancers. Mol Cancer 18: 83, 2019. https://doi.org/10.1186/s12943-019-0985-3
  2. Vokes EE, Weichselbaum RR, Lippman SM, Hong WK: Head and neck cancer. N Engl J Med 328: 184-194, 1993. https://doi.org/10.1056/NEJM199301213280306
  3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68: 394-424, 2018. https://doi.org/10.3322/caac.21492
  4. Dhanuthai K, Rojanawatsirivej S, Thosaporn W, et al.: Oral cancer: a multicenter study. Med Oral Patol Oral Cir Bucal 23: e23-e29, 2018. https://doi.org/10.4317/medoral.21999
  5. Kumar M, Nanavati R, Modi TG, Dobariya C: Oral cancer: etiology and risk factors: a review. J Cancer Res Ther 12: 458-463, 2016. https://doi.org/10.4103/0973-1482.186696
  6. Han JH, Kim EK, Lim SH, Kim CH: Literature review on the incidence and risk factor of oral cancer. J Dent Hyg Sci 12: 451-458, 2012.
  7. Bell RB, Kademani D, Homer L, Dierks EJ, Potter BE: Tongue cancer: Is there a difference in survival compared with other subsites in the oral cavity? J Oral Maxillofac Surg 65: 229-236, 2007. https://doi.org/10.1016/j.joms.2005.11.094
  8. Woolgar JA, Rogers SN, Lowe D, Brown JS, Vaughan ED: Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread. Oral Oncol 39: 130-137, 2003. https://doi.org/10.1016/S1368-8375(02)00030-1
  9. van Leeuwen FN, Giepmans BN, van Meeteren LA, Moolenaar WH: Lysophosphatidic acid: mitogen and motility factor. Biochem Soc Trans 31(Pt 6): 1209-1212, 2003. https://doi.org/10.1042/bst0311209
  10. Panupinthu N, Lee HY, Mills GB: Lysophosphatidic acid production and action: critical new players in breast cancer initiation and progression. Br J Cancer 102: 941-946, 2010. https://doi.org/10.1038/sj.bjc.6605588
  11. Hwang YS, Lee SK, Park KK, Chung WY: Secretion of IL-6 and IL-8 from lysophosphatidic acid-stimulated oral squamous cell carcinoma promotes osteoclastogenesis and bone resorption. Oral Oncol 48: 40-48, 2012. https://doi.org/10.1016/j.oraloncology.2011.08.022
  12. Cho KH: Lysophosphatidic acid-induced TWIST1 and slug expression in oral cancer cell invasion. J Dent Hyg Sci 17: 433-438, 2017. https://doi.org/10.17135/jdhs.2017.17.5.433
  13. Kim JY, Cho KH, Lee HY: Effect of resveratrol on oral cancer cell invasion induced by lysophosphatidic acid. J Dent Hyg Sci 18: 188-193, 2018. https://doi.org/10.17135/jdhs.2018.18.3.188
  14. Siveen KS, Sikka S, Surana R, et al.: Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. Biochim Biophys Acta 1845: 136-154, 2014. https://doi.org/10.1016/j.bbcan.2013.12.005
  15. Kim BH, Yi EH, Ye SK: Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment. Arch Pharm Res 39: 1085-1099, 2016. https://doi.org/10.1007/s12272-016-0795-8
  16. Zhao Y, Zhang J, Xia H, et al.: Stat3 is involved in the motility, metastasis and prognosis in lingual squamous cell carcinoma. Cell Biochem Funct 30: 340-346, 2012. https://doi.org/10.1002/cbf.2810
  17. Wang TY, Yu CC, Hsieh PL, Liao YW, Yu CH, Chou MY: GMI ablates cancer stemness and cisplatin resistance in oral carcinomas stem cells through IL-6/Stat3 signaling inhibition. Oncotarget 8: 70422-70430, 2017. https://doi.org/10.18632/oncotarget.19711
  18. Seo JH, Jeong KJ, Oh WJ, et al.: Lysophosphatidic acid induces STAT3 phosphorylation and ovarian cancer cell motility: their inhibition by curcumin. Cancer Lett 288: 50-56, 2010. https://doi.org/10.1016/j.canlet.2009.06.023
  19. Gkouveris I, Nikitakis N, Avgoustidis D, Karanikou M, Rassidakis G, Sklavounou A: ERK1/2, JNK and STAT3 activation and correlation with tumor differentiation in oral SCC. Histol Histopathol 32: 1065-1076, 2017. https://doi.org/10.14670/HH-11-868
  20. Zhou X, Ren Y, Liu A, et al.: STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo. Oncol Rep 31: 2173-2180, 2014. https://doi.org/10.3892/or.2014.3114
  21. Brusevold IJ, Tveteraas IH, Aasrum M, Odegard J, Sandnes DL, Christoffersen T: Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells. BMC Cancer 14: 432, 2014. https://doi.org/10.1186/1471-2407-14-432