DOI QR코드

DOI QR Code

자가포식작용과 구강암

Autophagy and Oral Cancer

  • Son, Seung Hwa (Department of Dental hygiene, Gangdong College) ;
  • Kim, Eun-Jung (Department of Biomedical Laboratory Science, Sangji University)
  • 투고 : 2017.07.29
  • 심사 : 2017.08.28
  • 발행 : 2017.08.30

초록

Autophagy는 세포 내에서 세포의 재활용과 다양한 스트레스에 세포 homeostasis와 survival에 중요한 역할을 한다. 최근 연구에서는 autophagy 활성이 oncogenes과 tumor suppressor genes의 발현이 조절됨으로써 암이 발달되거나 억제됨이 보고되고 있다. Autophagy의 유도는 정상세포에서는 암 발생을 예방하는데 관여하며, 손상된 세포사멸 기능을 가진 암세포에서는 특정세포사멸기전을 유발하는데 중요한 역할을 한다. 또한 autophagy 억제는 항암약물과 치료법에 저항을 나타내는 암세포를 민감하게 만들어 치료효능을 증가시킨다고 증명되고 있다. 그러나 cancer 치료에서의 autophagy의 역할은 아직까지 완전히 이해되지 않았다. Oral squamous cell carcinoma(OSCC)는 구강암의 90% 이상을 차지하고 있으며, 전세계적으로 6th 가장 흔한 암중의 하나로, 최근 2배 이상 증가하고 있으며 높은 mortality rate를 보이고 있다. 구강암에서의 autophagy의 역할은 다른 암들과 마찬가지로 종양형성의 초기 단계 동안 종양억제성을 보이나, 종양진행 동안은 종양세포 생존에 관여하는 두 가지의 기능을 나타내는 것으로 보고되고 있다. 본 리뷰에서는, 암에서의 autophagy의 조절에 대한 다양한 역할을 요약하고, 이를 바탕으로 효과적인 암 치료를 위한 유망한 target으로 autophagy의 가능성을 제시하고자 한다.

Autophagy plays an important role in cellular homeostasis and survival for cell recycling and various stresses within the cell. Recent studies have shown that autophagy activity modulates the expression of oncogene and tumor suppressor genes, leading to the development or suppression of cancer. Induction of autophagy is involved in preventing cancer development in normal cells and plays an important role in prompting a specific cell death mechanism in cancer cells with damaged cell death function. It is also known that autophagy inhibition increases the therapeutic efficacy by sensitizing cancer cells that are resistant to chemotherapy. However, the role of autophagy has not yet been fully understood in cancer treatment. Oral squamous cell carcinoma accounts for more than 90% of oral cancer and is the sixth most common cancer in the world. The incidence of oral cancer has increased by 50% over the last 20 years and the mortality rate is over 40% within 5 years after the onset. In oral cancers, the role of autophagy are described to look for tumor inhibitory in the early stages of tumor formation, like other cancers, indicating the dual functions involved in tumor cell survival include tumor progression stages. This review summarizes the various roles of autophagy in cancer cells and suggests the possibility of autophagy as a promising target for effective oral cancer therapy.

키워드

참고문헌

  1. Adhauliya, N., Kalappanavar, A. N., Ali, I. M. and Annigeri, R. G. 2016. Autophagy: A boon or bane in oral cancer. Oral Oncol. 61, 120-126. https://doi.org/10.1016/j.oraloncology.2016.09.001
  2. Ahn, M. Y., Ahn, S. G. and Yoon, J. H. 2011. Apicidin, a histone deaceylase inhibitor, induces both apoptosis and autophagy in human oral squamous carcinoma cells. Oral Oncol. 47, 1032-1038. https://doi.org/10.1016/j.oraloncology.2011.07.027
  3. Apel, A., Herr, I., Schwarz, H., Rodemann, H. P. and Mayer, A. 2008. Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy. Cancer Res. 68, 1485-1494. https://doi.org/10.1158/0008-5472.CAN-07-0562
  4. Bai, L. Y., Weng, J. R., Hu, J. L., Wang, D., Sargeant, A. M. and Chiu, C. F. 2013. G15, a GPR30 antagonist, induces apoptosis and autophagy in human oral squamous carcinoma cells. Chem. Biol. Interact. 206, 375-384. https://doi.org/10.1016/j.cbi.2013.10.014
  5. Cancer Genome Atlas Network. 2015. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517, 576-582. https://doi.org/10.1038/nature14129
  6. Carew, J. S., Nawrocki, S. T., Kahue, C. N., Zhang, H., Yang, C., Chung, L., Houghton, J. A., Huang, P., Giles, F. J. and Cleveland, J. L. 2007. Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl-mediated drug resistance. Blood 110, 313-322. https://doi.org/10.1182/blood-2006-10-050260
  7. Choi, K. S. 2012. Autophagy and cancer. Exp. Mol. Med. 44, 109-120. https://doi.org/10.3858/emm.2012.44.2.033
  8. Cho. T. J., Wee, S. W., Woo, V. H., Choi, J. I., Kim, S. J., Shin, H. I., Lee, J. H. and Park, H. R. 2014. Porphyromonas gingivalis-induced autophagy suppresses cell proliferation through G1 arrest in oral cancer cells. Arch. Oral Biol. 59, 370-378. https://doi.org/10.1016/j.archoralbio.2014.01.001
  9. Clarke, P. G. 1990. Developmental cell death: morphological diversity and multiple mechanisms. Anat. Embryol. (Berl) 181, 195-213.
  10. Cosway, B. and Lovat, P. 2016. The role of autophagy in squamous cell carcinoma of the head and neck. Oral Oncol. 54, 1-6. https://doi.org/10.1016/j.oraloncology.2015.12.007
  11. Degenhardt, K., Mathew, R., Beaudoin, B., Bray, K., Anderson, D., Chen, G., Mukherjee, C., Shi, Y., Gelinas, C., Fan, Y., Nelson, D. A., Jin, S. and White, E. 2006. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10, 51-64. https://doi.org/10.1016/j.ccr.2006.06.001
  12. Denton, D., Xu, T. and Kumar, S. 2015. Autophagy as a pro-death pathway. Immunol. Cell Biol. 93, 35-42. https://doi.org/10.1038/icb.2014.85
  13. Galluzzi, L., Vicencio, J. M., Kepp, O., Tasdemir, E., Maiuri, M. C. and Kroemer, G. 2008. To die or not to die: that is the autophagic question. Curr. Mol. Med. 8, 78-91. https://doi.org/10.2174/156652408783769616
  14. Gozuacik, D. and Kimchi, A. 2004. Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23, 2891-2906. https://doi.org/10.1038/sj.onc.1207521
  15. Kim, H. W. and Kim, S. A. 2014. Cinnamaldehyde derivative, 2'-benzoyloxycinnamaldehyde (BCA), Induces Apoptosis and Autophagy in Human Oral Squamous Carcinoma YD-10B Cells. Kor. J. Oral. Maxillofac. Pathol. 38, 247-256
  16. Jiang, L. C., Xin, Z. Y., Deborah, B., Zhang, J. S., Yuan, D. Y., Xu, K., Liu, X. B., Jiang, H. Q., Fan, Q. C., Zhang, B. and Li, K. Y. 2015. Inhibition of autophagy augments apoptosis in human oral squamous cell carcinoma under nutrient depletion. J. Oral Pathol. Med. 44, 361-366. https://doi.org/10.1111/jop.12250
  17. Karantza-Wadsworth, V., Patel, S., Kravchuk, O., Chen, G., Mathew, R., Jin, S. and White E. 2007. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 21, 1621-1635. https://doi.org/10.1101/gad.1565707
  18. Kimmelman, A. C. 2011. The dynamic nature of autophagy in cancer. Genes Dev. 25, 1999-2010. https://doi.org/10.1101/gad.17558811
  19. Klug, C., Berzaczy, D., Voracek, M. and Millesi, W. 2008. Preoperative chemoradiotherapy in the management of oral cancer: a review. J. Craniomaxillofac. Surg. 36, 75-88. https://doi.org/10.1016/j.jcms.2007.06.007
  20. Kujan, O., Glenny, A. M., Duxbury, J., Thakker, N. and Sloan, P. 2005. Evaluation of screening strategies for improving oral cancer mortality: a Cochrane systematic review. J. Dent. Educ. 69, 255-265.
  21. Leemans, C. R., Braakhuis, B. J. and Brakenhoff, R. H. 2011. The molecular biology of head and neck cancer. Nat. Rev. Cancer 11, 9-22. https://doi.org/10.1038/nrc2982
  22. Levine, B. and Klionsky, D. J. 2004. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463-477. https://doi.org/10.1016/S1534-5807(04)00099-1
  23. Levine, B. and Kroemer, G. 2008. Autophagy in the pathogenesis of disease. Cell 132, 27-42. https://doi.org/10.1016/j.cell.2007.12.018
  24. Li, Y. J., Lei, Y. H., Yao, N., Wang, C. R., Hu, N., Ye, W. C., Zhang, D. M. and Chen, Z. S. 2017. Autophagy and multidrug resistance in cancer. Chin. J. Cancer 36, 52. https://doi.org/10.1186/s40880-017-0219-2
  25. Liang, C., Lee, J. S., Inn, K. S., Gack, M. U., Li, Q., Roberts, E. A., Vergne, I., Deretic, V., Feng, P., Akazawa, C. and Jung, J. U. 2008. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat. Cell. Biol. 10, 776-787. https://doi.org/10.1038/ncb1740
  26. Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H. and Levine, B. 1999. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672-676. https://doi.org/10.1038/45257
  27. Lo-Muzio, L., Santarelli, A., Panzarella, V., Campisi, G., Carella, M., Ciavarella, D., Di-Cosola, M., Giannone, N. and Bascones, A. 2007. Oral squamous cell carcinoma and biological markers: an update on the molecules mainly involved in oral carcinogenesis. Minerva. Stomatol. 56, 341-347.
  28. Martin-Ezquerra, G., Salgado, R., Toll, A., Gilaberte, M., Baro, T., Alameda, Q., F., Yebenes, M., Sole, F., Garcia-Muret, M. and Espinet, B. 2010. Multiple genetic copy number alterations in oral squamous cell carcinoma: study of MYC, TP53, CCDN1, EGFR and ERBB2 status in primary and metastatic tumours. Br. J. Dermatol. 163, 1028-1035. https://doi.org/10.1111/j.1365-2133.2010.09947.x
  29. Mizushima, N., Levine, B., Cuervo, A. M. and Klionsky, D. J. 2008. Autophagy fights disease through cellular self-digestion. Nature 45, 1069-1075.
  30. Mizushima, N., Yoshimori, T. and Levine, B. 2010. Methods in mammalian autophagy research. Cell 140, 313-326. https://doi.org/10.1016/j.cell.2010.01.028
  31. Patil, S., Rao, R. S. and Raj, A. T. 2015. Dual role of autophagy in oral cancer. J. Int. Oral Health 7, i-ii.
  32. Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E. L., Mizushima, N., Ohsumi, Y., Cattoretti, G. and Levine, B. 2003. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 112, 1809-1820. https://doi.org/10.1172/JCI20039
  33. Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., Garcia-Arencibia, M., Green-Thompson, Z. W., Jimenez-Sanchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., Massey, D. C., Menzies, F. M., Moreau, K., Narayanan, U., Renna, M., Siddiqi, F. H., Underwood, B. R., Winslow, A. R. and Rubinsztein, D. C. 2010. Regulation of mammalian Autophagy in physiology and pathophysiology. Physiol. Rev. 90, 1383-1435. https://doi.org/10.1152/physrev.00030.2009
  34. Reef, S. and Kimchi, A. 2008. Nucleolar p19ARF, unlike mitochondrial smARF, is incapable of inducing p53-independent autophagy. Autophagy 4, 866-869. https://doi.org/10.4161/auto.6691
  35. Roepman, P., Wessels, L. F., Kettelarij, N., Kemmeren, P., Miles, A. J., Lijnzaadm, P., Tilanus, M. G., Koole, R., Hordijk, G. J., van der Vliet, P.C., Reinders, M. J., Slootweg, P. J. and Holstege, F. C. 2005. An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat. Genet. 37, 182-186. https://doi.org/10.1038/ng1502
  36. Rosenfeldt, M. T. and Ryan, K. M. 2009. The role of autophagy in tumour development and cancer therapy. Expert Rev. Mol. Med. 11, e36. https://doi.org/10.1017/S1462399409001306
  37. Rosenfeldt, M. T. and Ryan, K. M. 2011. The multiple roles of autophagy in cancer. Carcinogenesis 32, 955-963. https://doi.org/10.1093/carcin/bgr031
  38. Shaw, R. J. and Cantley, L. C. 2006. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441, 424-430. https://doi.org/10.1038/nature04869
  39. Singletary, K. and Milner, J. 2008. Diet, autophagy, and cancer: a review. Cancer Epidemiol. Biomarkers Prev. 17, 1596-1610. https://doi.org/10.1158/1055-9965.EPI-07-2917
  40. Soung, Y. H., Lee, J. W., Kim, S. Y., Jang, J., Park, Y. G., Park, W. S., Nam, S. W., Lee, J, Y., Yoo, N. J. and Lee, S. H. 2005. CASPASE-8 gene is inactivated by somatic mutations in gastric carcinomas. Cancer Res. 65, 815-821.
  41. Soussi, T. and Lozano, G. 2005. p53 mutation heterogeneity in cancer. Biochem. Biophys. Res. Commun. 331, 834-842. https://doi.org/10.1016/j.bbrc.2005.03.190
  42. Tasdemir, E., Maiuri, M. C., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D'Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., Nannmark, U., Samara, C., Pinton, P., Vicencio, J. M., Carnuccio, R., Moll, U. M., Madeo, F., Paterlini-Brechot, P., Rizzuto, R., Szabadkai, G., Pierron, G., Blomgren, K., Tavernarakis, N., Codogno, P., Cecconi, F and Kroemer, G. 2008. Regulation of autophagy by cytoplasmic p53. Nat. Cell. Biol. 10, 676-687. https://doi.org/10.1038/ncb1730
  43. White, E. 2012. Deconvoluting the context-dependent role for autophagy in cancer. Nat. Rev. Cancer 12, 401-410. https://doi.org/10.1038/nrc3262
  44. Yang, Z. and Klionsky, D. J. 2010. Eaten alive: a history of macroautophagy. Nat. Cell Biol. 12, 814-822. https://doi.org/10.1038/ncb0910-814
  45. Yang, Z. and Klionsky, D. J. 2010. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol. 22, 124-131. https://doi.org/10.1016/j.ceb.2009.11.014
  46. You, J., He, Z., Chen, L., Deng, G., Liu, W., Qin, L., Qiu, F. and Chen, X. 2010. CH05-10, a novel indinavir analog, is a broad-spectrum antitumor agent that induces cell cycle arrest, apoptosis, endoplasmic reticulum stress and autophagy. Cancer Sci. 101, 2644-2651. https://doi.org/10.1111/j.1349-7006.2010.01724.x