Research Progress of Claudins in Breast Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 QIANSong-ying , LIJian-yi ,  ZHANGWen-hai

Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China;

Corresponding author：

ZHANGWen-hai, Email: zhangwh@sj-hospital.org

Keywords：

Breast cancer; Claudins; Tight junction protein; Epithelial-mesenchymal transition

DOI：

10.7507/1007-9424.20160068

Video：

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Objective To understand research progress of influence of claudins on proliferation and activation for breast cancer. Method The relevant literatures of influence of claudins on proliferation and activation for breast cancer were retrieved and reviewed. Results The claudins had 24 members in mammals,claudin-13 was missing in human beings.Expression and distribution mode of the claudins possessed highly tissue-specific,and multiple proteins were expressed in many organizations.The expressions of claudins could be regulated from the levels of transcription and post-transcription,coordinately regulated by the transcription factor and post-synthetic modifications.Claudins were related to epithelial-mesenchymal transition.Now the studies were relatively clear those focused on claudin-1,-2,-4,-6,and other subtypes,and the expression of claudin-1 indicated the poor prognosis of tumor;claudin-2 was closely related to liver metastasis of breast cancer;claudin-4 was closely related to triple negative breast cancer;the function of claudin-6 in the breast cancer was controversial.In addition to the claudins mentioned above,other claudin members also played certain roles in normal breast and malignant breast tumors.Claudin-5 might participate in metastasis of breast cancer through N-WASP and ROCK signal pathway;CD-24 and claudin-7 immunodepression had a certain guiding significance on prognosis of invasive ductal carcinoma;the expressions of claudin-16 and HAPLN3 gene were remarkably increased in human breast cancer;Claudin-20 induced breast cancer cells into a subtype that possessed the high invasiveness and weakened the resis-tance of epithelial-mesenchymal transition.Recently,the claudin-low subtype was proposed,and it differed from other types of breast cancer in many aspects,and also it had a better prognosis than other types of triple negative breast cancer. Conclusions Claudin,being an important member of tight junction protein,is confirmed to be related to epithelial-mesenchymal transition.Claudins play important roles in dissociaton,activation,invasiveness,and metastasis of breast cancer,but there is no final conclusion which member contributes to invasiveness and metastasis of breast cancer.Moreover,there are opposite conclusions on some certain claudins members in breast cancer which might due to the different subtypes of breast cancer,so,further studies about the function of claudins in different subtypes are needed eagerly.

Citation： QIANSong-ying, LIJian-yi, ZHANGWen-hai. Research Progress of Claudins in Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(2): 248-252. doi: 10.7507/1007-9424.20160068 Copy

1.	Ding L, Lu Z, Lu Q, et al. The claudin family of proteins in human malignancy:a clinical perspective. Cancer Manag Res, 2013, 5:367-375.
2.	Furuse M, Fujita K, Hiiragi T, et al. Claudin-1 and -2:novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol, 1998, 141(7):1539-1550.
3.	Swisshelm K, Machl A, Planitzer S, et al. SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells, is a member of an epithelial membrane protein superfamily. Gene, 1999, 226(2):285-295.
4.	Markov AG. Claudins as tight junction proteins:the molecular element of paracellular transport. Ross Fiziol Zh Im I M Sechenova, 2013, 99(2):175-195.
5.	Lal-Nag M, Morin PJ. The claudins. Genome Biol, 2009, 10(8):235.
6.	Krause G, Winkler L, Mueller SL, et al. Structure and function of claudins. Biochim Biophys Acta, 2008, 1778(3):631-645.
7.	Medici D, Hay ED, Goodenough DA. Cooperation between snail and LEF-1 transcription factors is essential for TGF-beta1-induced epithelial-mesenchymal transition. Mol Biol Cell, 2006, 17(4):1871-1879.
8.	Ikari A, Atomi K, Yamazaki Y, et al. Hyperosmolarity-induced up-regulation of claudin-4 mediated by NADPH oxidase-dependent H2O2 production and Sp1/c-Jun cooperation. Biochim Biophys Acta, 2013, 1833(12):2617-2627.
9.	Kwon MJ. Emerging roles of claudins in human cancer. Int J Mol Sci, 2013, 14(9):18148-18180.
10.	Arima Y, Inoue Y, Shibata T, et al. Rb depletion results in deregula-tion of E-cadherin and induction of cellular pheno-typic changes that are characteristic of the epithelial-to-mes-enchymal transition. Cancer Res, 2008, 68(13):5104-5112.
11.	Morel AP, Hinkal GW, Thomas C, et al. EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice. PLoS Genet, 2012, 8(5):e1002723.
12.	Taube JH, Herschkowitz JI, Komurov K, et al. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci U S A, 2010, 107(35):15449-15454.
13.	Akasaka H, Sato F, Morohashi S, et al. Anti-apoptotic effect of claudin-1 in tamoxifen-treated human breast cancer MCF-7 cells. BMC Cancer, 2010, 10:548.
14.	Blanchard AA, Ma X, Dueck KJ, et al. Claudin 1 expression in basal-like breast cancer is related to patient age. BMC Cancer, 2013, 13:268.
15.	Di Cello F, Cope L, Li H, et al. Methylation of the claudin 1 promoter is associated with loss of expression in estrogen receptor positive breast cancer. PLoS One, 2013, 8(7):e68630.
16.	Hou J, Wang Z, Xu H, et al. Stanniocalicin 2 suppresses breast cancer cell migration and invasion via the PKC/claudin-1-mediated signaling. PLoS One, 2015, 10(4):e0122179.
17.	Ma F, Ding X, Fan Y, et al. A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer. PLoS One, 2014, 9(11):e112765.
18.	Tabariès S, Dupuy F, Dong Z, et al. Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes. Mol Cell Biol, 2012, 32(15):2979-2991.
19.	Tabariès S, Annis MG, Hsu BE, et al. Lynmodulates claudin-2 expre-ssion and is a therapeutic target for breast cancer liver metastasis. Oncotarget, 2015 Mar 25.[Epub ahead of print]. PubMed PMID:25823815.
20.	Kimbung S, Kovács A, Bendahl PO, et al. Claudin-2 is an indepen-dent negative prognostic factor in breast cancer and specifically predicts early liver recurrences. Mol Oncol, 2014, 8(1):119-128.
21.	Tabariès S, Dong Z, Annis MG, et al. Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes. Oncogene, 2011, 30(11):1318-1328.
22.	Kolokytha P, Yiannou P, Keramopoulos D, et al. Claudin-3 and claudin-4:distinct prognostic significance in triple-negative and luminal breast cancer. Appl Immunohistochem Mol Morphol, 2014, 22(2):125-131.
23.	Abd-Elazeem MA, Abd-Elazeem MA. Claudin 4 expression in triple-negative breast cancer:correlation with androgen receptors and Ki-67 expression. Ann Diagn Pathol, 2015, 19(1):37-42.
24.	Cui YF, Liu AH, An DZ, et al. Claudin-4 is required for vasculogenic mimicry formation in human breast cancer cells. Oncotarget, 2015 Mar 14.[Epub ahead of print]. PubMed PMID:25871476.
25.	Saeki R, Kondoh M, Kakutani H, et al. A novel tumor-targeted therapy using a claudin-4-targeting molecule. Mol Pharmacol, 2009, 76(4):918-926.
26.	Kato-Nakano M, Suzuki M, Kawamoto S, et al. Characterization and evaluation of the antitumour activity of a dual-targeting mono-clonal antibody against claudin-3 and claudin-4. Anticancer Res, 2010, 30(11):4555-4562.
27.	Tsukita S, Furuse M. Occludin and claudins in tight-junction strands: leading or supporting players? Trends Cell Biol, 1999, 9(7):268-273.
28.	Troy TC, Turksen K. Epidermal lineage. Methods Mol Biol, 2002, 185(3):229-253.
29.	Offner S, Hekele A, Teichmann U, et al. Epithelial tight junction proteins as potential antibody targets for pancarcinoma therapy. Cancer Immunol Immunother, 2005, 54(5):431-445.
30.	Soini Y. Claudins 2, 3, 4, and 5 in Paget's disease and breast carci-noma. Hum Pathol, 2004, 35(12):1531-1536.
31.	Soini Y. Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology, 2005, 46(5):551-560.
32.	Sobel G, Páska C, Szabó I, et al. Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma. Hum Pathol, 2005, 36(2):162-169.
33.	Wu Q, Liu Y, Ren Y, et al. Tight junction protein, claudin-6, downregulates the malignant phenotype of breast carcinoma. Eur J Cancer Prev, 2010, 19(3):186-194.
34.	Quan C, Lu SJ. Identification of genes preferentially expressed in mammary epithelial cells of Copenhagen rat using subtractive hybri-dization and microarrays. Carcinogenesis, 2003, 24(10):1593-1599.
35.	Osanai M, Murata M, Chiba H, et al. Epigenetic silencing of claudin-6 promotes anchorage-independent growth of breast carcinoma cells. Cancer Sci, 2007, 98(10):1557-1562.
36.	Liu YF, Wu Q, Ren Y, et al. Role of estrogen receptor-α in the regulation of claudin-6 expression in breast cancer cells. J Breast Cancer, 2011, 14(1):20-27.
37.	Wu Q, Liu X, Liu YF, et al. Inhibition of p38 activity reverses claudin-6 induced cell apoptosis, invasion, and migration. Chin Med J (Engl), 2013, 126(18):3539-3544.
38.	Escudero-Esparza A, Jiang WG, Martin TA. Claudin-5 is involved in breast cancer cell motility through the N-WASP and ROCK signalling pathways. J Exp Clin Cancer Res. 2012, 31:43.
39.	Bernardi MA, Logullo AF, Pasini FS, et al. Prognostic significance of CD24 and claudin-7 immunoexpression in ductal invasive breast cancer. Oncol Rep, 2012, 27(1):28-38.
40.	Kuo SJ, Chien SY, Lin C, et al. Significant elevation of CLDN16 and HAPLN3 gene expression in human breast cancer. Oncol Rep, 2010, 24(3):759-766.
41.	Martin TA, Lane J, Ozupek H, et al. Claudin-20 promotes an aggressive phenotype in human breast cancer cells. Tissue Barriers, 2013, 1(3):e26518.
42.	Sabatier R, Finetti P, Guille A, et al. Claudin-low breast cancers:clinical, pathological, molecular and prognostic characterization. Mol Cancer, 2014, 13:228.
43.	Knezevic J, Pfefferle AD, Petrovic I, et al. Expression of miR-200c in claudin-low breast cancer alters stem cell functionality, enhances chemosensitivity and reduces metastatic potential. Oncogene, 2015 Mar 9. doi:10.1038/onc.2015.48.[Epub ahead of print]. PubMed PMID:25746005.
44.	Roll JD, Rivenbark AG, Sandhu R, et al. Dysregulation of the epigenome in triple-negative breast cancers:basal-like and claudin-low breast cancers Express aberrant DNA hypermethylation. Exp Mol Pathol, 2013, 95(3):276-287.
45.	Gerhard R, Ricardo S, Albergaria A, et al. Immunohistochemical features of claudin-low intrinsic subtype in metaplastic breast carcinomas. Breast, 2012, 21(3):354-360.
46.	Tudoran O, Soritau O, Balacescu L, et al. Regulation of stem cells-related signaling pathways in response to doxorubicin treatment in Hs578T triple-negative breast cancer cells. Mol Cell Biochem, 2015 Jul 18. Epub ahead of print]. PubMed PMID:26187676.

1. Ding L, Lu Z, Lu Q, et al. The claudin family of proteins in human malignancy:a clinical perspective. Cancer Manag Res, 2013, 5:367-375.
2. Furuse M, Fujita K, Hiiragi T, et al. Claudin-1 and -2:novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol, 1998, 141(7):1539-1550.
3. Swisshelm K, Machl A, Planitzer S, et al. SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells, is a member of an epithelial membrane protein superfamily. Gene, 1999, 226(2):285-295.
4. Markov AG. Claudins as tight junction proteins:the molecular element of paracellular transport. Ross Fiziol Zh Im I M Sechenova, 2013, 99(2):175-195.
5. Lal-Nag M, Morin PJ. The claudins. Genome Biol, 2009, 10(8):235.
6. Krause G, Winkler L, Mueller SL, et al. Structure and function of claudins. Biochim Biophys Acta, 2008, 1778(3):631-645.
7. Medici D, Hay ED, Goodenough DA. Cooperation between snail and LEF-1 transcription factors is essential for TGF-beta1-induced epithelial-mesenchymal transition. Mol Biol Cell, 2006, 17(4):1871-1879.
8. Ikari A, Atomi K, Yamazaki Y, et al. Hyperosmolarity-induced up-regulation of claudin-4 mediated by NADPH oxidase-dependent H2O2 production and Sp1/c-Jun cooperation. Biochim Biophys Acta, 2013, 1833(12):2617-2627.
9. Kwon MJ. Emerging roles of claudins in human cancer. Int J Mol Sci, 2013, 14(9):18148-18180.
10. Arima Y, Inoue Y, Shibata T, et al. Rb depletion results in deregula-tion of E-cadherin and induction of cellular pheno-typic changes that are characteristic of the epithelial-to-mes-enchymal transition. Cancer Res, 2008, 68(13):5104-5112.
11. Morel AP, Hinkal GW, Thomas C, et al. EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice. PLoS Genet, 2012, 8(5):e1002723.
12. Taube JH, Herschkowitz JI, Komurov K, et al. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci U S A, 2010, 107(35):15449-15454.
13. Akasaka H, Sato F, Morohashi S, et al. Anti-apoptotic effect of claudin-1 in tamoxifen-treated human breast cancer MCF-7 cells. BMC Cancer, 2010, 10:548.
14. Blanchard AA, Ma X, Dueck KJ, et al. Claudin 1 expression in basal-like breast cancer is related to patient age. BMC Cancer, 2013, 13:268.
15. Di Cello F, Cope L, Li H, et al. Methylation of the claudin 1 promoter is associated with loss of expression in estrogen receptor positive breast cancer. PLoS One, 2013, 8(7):e68630.
16. Hou J, Wang Z, Xu H, et al. Stanniocalicin 2 suppresses breast cancer cell migration and invasion via the PKC/claudin-1-mediated signaling. PLoS One, 2015, 10(4):e0122179.
17. Ma F, Ding X, Fan Y, et al. A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer. PLoS One, 2014, 9(11):e112765.
18. Tabariès S, Dupuy F, Dong Z, et al. Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes. Mol Cell Biol, 2012, 32(15):2979-2991.
19. Tabariès S, Annis MG, Hsu BE, et al. Lynmodulates claudin-2 expre-ssion and is a therapeutic target for breast cancer liver metastasis. Oncotarget, 2015 Mar 25.[Epub ahead of print]. PubMed PMID:25823815.
20. Kimbung S, Kovács A, Bendahl PO, et al. Claudin-2 is an indepen-dent negative prognostic factor in breast cancer and specifically predicts early liver recurrences. Mol Oncol, 2014, 8(1):119-128.
21. Tabariès S, Dong Z, Annis MG, et al. Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes. Oncogene, 2011, 30(11):1318-1328.
22. Kolokytha P, Yiannou P, Keramopoulos D, et al. Claudin-3 and claudin-4:distinct prognostic significance in triple-negative and luminal breast cancer. Appl Immunohistochem Mol Morphol, 2014, 22(2):125-131.
23. Abd-Elazeem MA, Abd-Elazeem MA. Claudin 4 expression in triple-negative breast cancer:correlation with androgen receptors and Ki-67 expression. Ann Diagn Pathol, 2015, 19(1):37-42.
24. Cui YF, Liu AH, An DZ, et al. Claudin-4 is required for vasculogenic mimicry formation in human breast cancer cells. Oncotarget, 2015 Mar 14.[Epub ahead of print]. PubMed PMID:25871476.
25. Saeki R, Kondoh M, Kakutani H, et al. A novel tumor-targeted therapy using a claudin-4-targeting molecule. Mol Pharmacol, 2009, 76(4):918-926.
26. Kato-Nakano M, Suzuki M, Kawamoto S, et al. Characterization and evaluation of the antitumour activity of a dual-targeting mono-clonal antibody against claudin-3 and claudin-4. Anticancer Res, 2010, 30(11):4555-4562.
27. Tsukita S, Furuse M. Occludin and claudins in tight-junction strands: leading or supporting players? Trends Cell Biol, 1999, 9(7):268-273.
28. Troy TC, Turksen K. Epidermal lineage. Methods Mol Biol, 2002, 185(3):229-253.
29. Offner S, Hekele A, Teichmann U, et al. Epithelial tight junction proteins as potential antibody targets for pancarcinoma therapy. Cancer Immunol Immunother, 2005, 54(5):431-445.
30. Soini Y. Claudins 2, 3, 4, and 5 in Paget's disease and breast carci-noma. Hum Pathol, 2004, 35(12):1531-1536.
31. Soini Y. Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology, 2005, 46(5):551-560.
32. Sobel G, Páska C, Szabó I, et al. Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma. Hum Pathol, 2005, 36(2):162-169.
33. Wu Q, Liu Y, Ren Y, et al. Tight junction protein, claudin-6, downregulates the malignant phenotype of breast carcinoma. Eur J Cancer Prev, 2010, 19(3):186-194.
34. Quan C, Lu SJ. Identification of genes preferentially expressed in mammary epithelial cells of Copenhagen rat using subtractive hybri-dization and microarrays. Carcinogenesis, 2003, 24(10):1593-1599.
35. Osanai M, Murata M, Chiba H, et al. Epigenetic silencing of claudin-6 promotes anchorage-independent growth of breast carcinoma cells. Cancer Sci, 2007, 98(10):1557-1562.
36. Liu YF, Wu Q, Ren Y, et al. Role of estrogen receptor-α in the regulation of claudin-6 expression in breast cancer cells. J Breast Cancer, 2011, 14(1):20-27.
37. Wu Q, Liu X, Liu YF, et al. Inhibition of p38 activity reverses claudin-6 induced cell apoptosis, invasion, and migration. Chin Med J (Engl), 2013, 126(18):3539-3544.
38. Escudero-Esparza A, Jiang WG, Martin TA. Claudin-5 is involved in breast cancer cell motility through the N-WASP and ROCK signalling pathways. J Exp Clin Cancer Res. 2012, 31:43.
39. Bernardi MA, Logullo AF, Pasini FS, et al. Prognostic significance of CD24 and claudin-7 immunoexpression in ductal invasive breast cancer. Oncol Rep, 2012, 27(1):28-38.
40. Kuo SJ, Chien SY, Lin C, et al. Significant elevation of CLDN16 and HAPLN3 gene expression in human breast cancer. Oncol Rep, 2010, 24(3):759-766.
41. Martin TA, Lane J, Ozupek H, et al. Claudin-20 promotes an aggressive phenotype in human breast cancer cells. Tissue Barriers, 2013, 1(3):e26518.
42. Sabatier R, Finetti P, Guille A, et al. Claudin-low breast cancers:clinical, pathological, molecular and prognostic characterization. Mol Cancer, 2014, 13:228.
43. Knezevic J, Pfefferle AD, Petrovic I, et al. Expression of miR-200c in claudin-low breast cancer alters stem cell functionality, enhances chemosensitivity and reduces metastatic potential. Oncogene, 2015 Mar 9. doi:10.1038/onc.2015.48.[Epub ahead of print]. PubMed PMID:25746005.
44. Roll JD, Rivenbark AG, Sandhu R, et al. Dysregulation of the epigenome in triple-negative breast cancers:basal-like and claudin-low breast cancers Express aberrant DNA hypermethylation. Exp Mol Pathol, 2013, 95(3):276-287.
45. Gerhard R, Ricardo S, Albergaria A, et al. Immunohistochemical features of claudin-low intrinsic subtype in metaplastic breast carcinomas. Breast, 2012, 21(3):354-360.
46. Tudoran O, Soritau O, Balacescu L, et al. Regulation of stem cells-related signaling pathways in response to doxorubicin treatment in Hs578T triple-negative breast cancer cells. Mol Cell Biochem, 2015 Jul 18. Epub ahead of print]. PubMed PMID:26187676.

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