リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Upregulation of cyclase-associated actin cytoskeleton regulatory protein 2 in epithelial ovarian cancer correlates with aggressive histologic types and worse outcomes (本文)」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Upregulation of cyclase-associated actin cytoskeleton regulatory protein 2 in epithelial ovarian cancer correlates with aggressive histologic types and worse outcomes (本文)

安達, 将隆 慶應義塾大学

2020.09.21

概要

Objective: Cyclase-associated actin cytoskeleton regulatory protein 2 (CAP2) regulates actin dynamics to control cell cycles and cell migration. CAP2 overexpression contributes to cancer progression in several tumor types; however, the role of CAP2 expression in ovarian cancer remains unclear. This study aimed to clarify the significance of CAP2 expression in epithelial ovarian tumor. Methods: We evaluated CAP2 expression in ovarian cancer cell lines using quantitative real-time polymerase chain reaction, western blotting and immunocytochemistry and examined the effect of CAP2 silencing in migration and proliferation assays. CAP2 immunohistochemistry was conducted using tissue specimens from 432 ovarian carcinoma patients; a further 55 borderline and benign 65 lesions were analyzed. CAP2 expression levels were defined as low, intermediate or high, for correlation analysis with clinicopathological factors.

Results: CAP2 expression was significantly higher in cell lines from Type II ovarian cancer than in those in Type I, and knockdown of CAP2 showed decreased migration and proliferation. Higher levels of CAP2 expression in human tissues were associated with Type II histology, residual lesion, lymph node metastasis, ascites cytology and higher clinical stage. High CAP2 expression levels were observed in 26 (23.4%) of 111 Type II ovarian cancers and in 16 (5.0%) of 321 Type I cancers but not in any borderline or benign lesions. Multivariate analyses showed that CAP2 expression in ovarian cancer is an independent prognostic factor for recurrence-free survival (P = 0.019).

Conclusion: CAP2 expression is upregulated in aggressive histologic types of epithelial ovarian cancer and serves as a novel prognostic biomarker for patient survival.

Key words: cyclase-associated actin cytoskeleton regulatory protein 2, epithelial ovarian cancer, Type I and Type II ovarian cancer, biomarker

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mor- tality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424.

2. Torre LA, Trabert B, DeSantis CE et al. Ovarian cancer statistics, 2018. CA Cancer J Clin 2018;68:284–96.

3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7–30.

4. Cho KR, Shih IM. Ovarian cancer. Annu Rev Pathol 2009;4:287–313.

5. Karst AM, Drapkin R. Ovarian cancer pathogenesis: a model in evolution. J Oncol 2010;2010:932371.

6. Lim D, Oliva E. Precursors and pathogenesis of ovarian carcinoma. Pathology 2013;45:229–42.

7. Prat J. New insights into ovarian cancer pathology. Ann Oncol 2012;23:x111–7.

8. Kurman RJ, Shih IM. Molecular pathogenesis and extraovarian ori- gin of epithelial ovarian cancer – shifting the paradigm. Hum Pathol 2011;42:918–31.

9. Kurman RJ, Shih IM. The dualistic model of ovarian carcinogenesis: revisited, revised, and expanded. Am J Pathol 2016;186:733–47.

10. Kurman RJ, Shih IM. The origin and pathogenesis of epithelial ovar- ian cancer: a proposed unifying theory. Am J Surg Pathol 2010;34: 433–43.

11. Kurman RJ, Shih IM. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol 2008;27:151–60.

12. Kaldawy A, Segev Y, Lavie O, Auslender R, Sopik V, Narod SA. Low-grade serous ovarian cancer: a review. Gynecol Oncol 2016;143:433–8.

13. Koshiyama M, Matsumura N, Konishi I. Subtypes of ovarian cancer and ovarian cancer screening. Diagnostics (Basel) 2017;7.

14. Matias-Guiu X, Stewart CJR. Endometriosis-associated ovarian neoplasia. Pathology 2018;50:190–204.

15. Sadlecki P, Walentowicz-Sadlecka M, Grabiec M. Molecular diagnosis in type I epithelial ovarian cancer. Ginekol Pol 2017;88:692–7.

16. Skirnisdottir I, Seidal T, Akerud H. Differences in clinical and biological features between type I and type II tumors in FIGO stages I-II epithelial ovarian carcinoma. Int J Gynecol Cancer 2015;25:1239–47.

17. Murakami R, Matsumura N, Mandai M et al. Establishment of a novel histopathological classification of high-grade serous ovarian carcinoma correlated with prognostically distinct gene expression subtypes. Am J Pathol 2016;186:1103–13.

18. Smolle E, Taucher V, Pichler M, Petru E, Lax S, Haybaeck J. Tar- geting signaling pathways in epithelial ovarian cancer. Int J Mol Sci 2013;14:9536–55.

19. Rojas V, Hirshfield KM, Ganesan S, Rodriguez-Rodriguez L. Molecular characterization of epithelial ovarian cancer: implications for diagnosis and treatment. Int J Mol Sci 2016;17.

20. Salazar C, Campbell IG, Gorringe KL. When is “type I” ovarian can- cer not “type I”? Indications of an out-dated dichotomy. Front Oncol 2018;8:654.

21. Yano M, Yasuda M, Sakaki M et al. Association of histone deacetylase expression with histology and prognosis of ovarian cancer. Oncol Lett 2018;15:3524–31.

22. Takenaka M, Kobel M, Garsed DW et al. Survival following chemother- apy in ovarian clear cell carcinoma is not associated with patholog- ical misclassification of tumor histotype. Clin Cancer Res 2019;25: 3962–73.

23. Kotila T, Kogan K, Enkavi G et al. Structural basis of actin monomer re-charging by cyclase-associated protein. Nat Commun 2018;9: 1892.

24. Ono S. The role of cyclase-associated protein in regulating actin fila- ment dynamics - more than a monomer-sequestration factor. J Cell Sci 2013;126:3249–58.

25. Ono S. Mechanism of depolymerization and severing of actin fila- ments and its significance in cytoskeletal dynamics. Int Rev Cytol 2007;258:1–82.

26. Bertling E, Hotulainen P, Mattila PK, Matilainen T, Salminen M, Lappalainen P. Cyclase-associated protein 1 (CAP1) promotes cofilin- induced actin dynamics in mammalian nonmuscle cells. Mol Biol Cell 2004;15:2324–34.

27. Bertling E, Quintero-Monzon O, Mattila PK, Goode BL, Lappalainen P. Mechanism and biological role of profilin-Srv2/CAP interaction. J Cell Sci 2007;120:1225–34.

28. Jansen S, Collins A, Golden L, Sokolova O, Goode BL. Structure and mechanism of mouse cyclase-associated protein (CAP1) in regulating actin dynamics. J Biol Chem 2014;289:30732–42.

29. Kakurina GV, Kolegova ES, Kondakova IV. Adenylyl cyclase-associated protein 1: structure, regulation, and participation in cellular processes. Biochemistry (Mosc) 2018;83:45–53.

30. Normoyle KP, Brieher WM. Cyclase-associated protein (CAP) acts directly on F-actin to accelerate cofilin-mediated actin severing across the range of physiological pH. J Biol Chem 2012;287:35722–32.

31. Zhou GL, Zhang H, Field J. Mammalian CAP (cyclase-associated protein) in the world of cell migration: roles in actin filament dynamics and beyond. Cell Adh Migr 2014;8:55–9.

32. Shibata R, Mori T, Du W et al. Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis. Clin Cancer Res 2006;12:5363–8.

33. Sakamoto M, Effendi K, Masugi Y. Molecular diagnosis of multistage hepatocarcinogenesis. Jpn J Clin Oncol 2010;40:891–6.

34. Sakamoto M. Early HCC: diagnosis and molecular markers. J Gastroen- terol 2009;44:108–11.

35. Sakamoto M, Mori T, Masugi Y, Effendi K, Rie I, Du W. Candidate molec- ular markers for histological diagnosis of early hepatocellular carcinoma. Intervirology 2008;51:42–5.

36. Fu J, Li M, Wu DC, Liu LL, Chen SL, Yun JP. Increased expression of CAP2 indicates poor prognosis in hepatocellular carcinoma. Transl Oncol 2015;8:400–6.

37. Masugi Y, Tanese K, Emoto K et al. Overexpression of adenylate cyclase- associated protein 2 is a novel prognostic marker in malignant melanoma. Pathol Int 2015;65:627–34.

38. Xu L, Peng S, Huang Q et al. Expression status of cyclase-associated protein 2 as a prognostic marker for human breast cancer. Oncol Rep 2016;36:1981–8.

39. Li L, Fu LQ, Wang HJ, Wang YY. CAP2 is a valuable biomarker for diagnosis and prognostic in patients with gastric cancer. Pathol Oncol Res 2018.

40. Xie S, Shen C, Tan M, Li M, Song X, Wang C. Systematic analysis of gene expression alterations and clinical outcomes of adenylate cyclase- associated protein in cancer. Oncotarget 2017;8:27216–39.

41. Domcke S, Sinha R, Levine DA, Sander C, Schultz N. Evaluating cell lines as tumour models by comparison of genomic profiles. Nat Commun 2013;4:2126.

42. Nozawa S, Tsukazaki K, Sakayori M, Jeng CH, Iizuka R. Establishment of a human ovarian clear cell carcinoma cell line (RMG-I) and its single cell cloning – with special reference to the stem cell of the tumor. Hum Cell 1988;1:426–35.

43. Sakayori M, Nozawa S, Udagawa Y et al. Biological properties of two newly established cell lines (RMUG-S, RMUG-L) from a human ovarian mucinous cystadenocarcinoma. Hum Cell 1990;3:52–6 (in Japanese).

44. Effendi K, Yamazaki K, Mori T, Masugi Y, Makino S, Sakamoto M. Involvement of hepatocellular carcinoma biomarker, cyclase-associated protein 2 in zebrafish body development and cancer progression. Exp Cell Res 2013;319:35–44.

45. Krause M, Gautreau A. Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nat Rev Mol Cell Biol 2014;15:577–90.

46. Hall A. The cytoskeleton and cancer. Cancer Metastasis Rev 2009;28:5–14.

47. Jin ZL, Jo YJ, Namgoong S, Kim NH. CAP1-mediated actin cycling via ADF/cofilin proteins is essential for asymmetric division in mouse oocytes. J Cell Sci 2018;131.

48. Mattila PK, Lappalainen P. Filopodia: molecular architecture and cellular functions. Nat Rev Mol Cell Biol 2008;9:446–54.

49. Yamazaki K, Takamura M, Masugi Y et al. Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. Lab Invest 2009;89:425–32.

50. Mohammed MA, Moustafa Omar N, Mohammed SA, Galal Deiab A. Identification of cyclase-associated protein-2 as a novel biomarker for early- stage hepatocellular carcinoma. J Clin Gastroenterol Hepatol 2017;01.

51. Saini U, Naidu S, ElNaggar AC et al. Elevated STAT3 expression in ovarian cancer ascites promotes invasion and metastasis: a potential therapeutic target. Oncogene 2017;36:168–81.

52. Yamamoto CM, Oakes ML, Murakami T, Muto MG, Berkowitz RS, Ng SW. Comparison of benign peritoneal fluid- and ovarian cancer ascites- derived extracellular vesicle RNA biomarkers. J Ovarian Res 2018;11:20.

53. Kim S, Kim B, Song YS. Ascites modulates cancer cell behavior, contributing to tumor heterogeneity in ovarian cancer. Cancer Sci 2016;107:1173–8.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文
を
一発検索！

この論文の関連論文を見る