Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Induction of Integrin Signaling by Steroid Sulfatase in Human Cervical Cancer Cells

  • Received : 2016.07.17
  • Accepted : 2016.10.04
  • Published : 2017.05.01
Download PDF
⟨ Previous Next ⟩

Abstract

Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin ${\beta}1$ and fibronectin, a ligand of integrin ${\alpha}5{\beta}1$. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin ${\beta}1$ and fibronectin. Further, STS expression and DHEA treatment enhanced phosphorylation of focal adhesion kinase (FAK) at the Tyr 925 residue. Moreover, increased phosphorylation of ERK at Thr 202 and Tyr 204 residues by STS indicates that STS activates the MAPK/ERK pathway. In conclusion, these results suggest that STS expression and DHEA treatment may enhance MAPK/ERK signaling through up-regulation of integrin ${\beta}1$ and activation of FAK.

Keywords

References

  1. Abulafia, O., Lee, Y. C., Wagreich, A., Economos, K., Serur, E. and Nacharaju, V. L. (2009) Sulfatase activity in normal and neoplastic endometrium. Gynecol. Obstet. Invest. 67, 57-60. https://doi.org/10.1159/000161571
  2. Ahn, H. N., Jeong, S. Y., Bae, G. U., Chang, M., Zhang, D., Liu, X., Pei, Y., Chin, Y. W., Lee, J., Oh, S. R. and Song, Y. S. (2014) Selective estrogen receptor modulation by Larrea nitida on MCF-7 cell proliferation and immature rat uterus. Biomol. Ther. (Seoul) 22, 347-354. https://doi.org/10.4062/biomolther.2014.050
  3. Baglietto, L., Severi, G., English, D. R., Krishnan, K., Hopper, J. L., McLean, C., Morris, H. A., Tilley, W. D. and Giles, G. G. (2010) Circulating steroid hormone levels and risk of breast cancer for postmenopausal women. Cancer Epidemiol. Biomarkers Prev. 19, 492-502. https://doi.org/10.1158/1055-9965.EPI-09-0532
  4. Cai, C., Chen, S., Ng, P., Bubley, G. J., Nelson, P. S., Mostaghel, E. A., Marck, B., Matsumoto, A. M., Simon, N. I., Wang, H., Chen, S. and Balk, S. P. (2011) Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors. Cancer Res. 71, 6503-6513. https://doi.org/10.1158/0008-5472.CAN-11-0532
  5. Cheung, P. F., Wong, C. K., Ip, W. K. and Lam, C. W. (2008) FAK-mediated activation of ERK for eosinophil migration: a novel mechanism for infection-induced allergic inflammation. Int. Immunol. 20, 353-363. https://doi.org/10.1093/intimm/dxm146
  6. Chumsri, S., Howes, T., Bao, T., Sabnis, G. and Brodie, A. (2011) Aromatase, aromatase inhibitors, and breast cancer. J. Steroid Biochem. Mol. Biol. 125, 13-22. https://doi.org/10.1016/j.jsbmb.2011.02.001
  7. Cid, M. C., Esparza, J., Schnaper, H. W., Juan, M., Yague, J., Grant, D. S., Urbano-Marquez, A., Hoffman, G. S. and Kleinman, H. K. (1999) Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function. Angiogenesis 3, 271-280. https://doi.org/10.1023/A:1009023329294
  8. Cuzick, J., Sestak, I., Baum, M., Buzdar, A., Howell, A., Dowsett, M. and Forbes, J. F. (2010) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 11, 1135-1141. https://doi.org/10.1016/S1470-2045(10)70257-6
  9. Dent, S. F., Gaspo, R., Kissner, M. and Pritchard, K. I. (2011) Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer. Breast Cancer Res. Treat. 126, 295-310. https://doi.org/10.1007/s10549-011-1351-3
  10. Evans, T. R., Rowlands, M. G., Law, M. and Coombes, R. C. (1994) Intratumoral oestrone sulphatase activity as a prognostic marker in human breast carcinoma. Br. J. Cancer 69, 555-561. https://doi.org/10.1038/bjc.1994.101
  11. Evans, T. R., Rowlands, M. G., Silva, M. C., Law, M. and Coombes, R. C. (1993) Prognostic significance of aromatase and estrone sulfatase enzymes in human breast cancer. J. Steroid Biochem. Mol. Biol. 44, 583-587. https://doi.org/10.1016/0960-0760(93)90263-V
  12. Fournier, M. A. and Poirier, D. (2009) Estrogen formation in endometrial and cervix cancer cell lines: Involvement of aromatase, steroid sulfatase and $17{\beta}$-hydroxysteroid dehydrogenases (types 1, 5, 7 and 12). Mol. Cell. Endocrinol. 301, 142-145. https://doi.org/10.1016/j.mce.2008.08.027
  13. Gera, J. F., Mellinghoff, I. K., Shi, Y., Rettig, M. B., Tran, C., Hsu, J. H., Sawyers, C. L. and Lichtenstein, A. K. (2004) AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression. J. Biol. Chem. 279, 2737-2746. https://doi.org/10.1074/jbc.M309999200
  14. Guo, W. and Giancotti, F. G. (2004) Integrin signalling during tumour progression. Nat. Rev. Mol. Cell Biol. 5, 816-826. https://doi.org/10.1038/nrm1490
  15. Haning, R. V., Hackett, R. J., Boothroid, R. I. and Canick, J. A. (1990) Steroid sulfatase activity in the human ovarian corpus luteum, stroma and follicle: comparison to activity in other tissues and the placenta. J. Steroid Biochem. 36, 175-179. https://doi.org/10.1016/0022-4731(90)90127-E
  16. Hynes, R. O. (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110, 673-687. https://doi.org/10.1016/S0092-8674(02)00971-6
  17. Im, H. J., Park, N. H., Kwon, Y. J., Shin, S., Kim, D. and Chun, Y. J. (2012) Bacterial lipopolysaccharides induce steroid sulfatase expression and cell migration through IL-6 pathway in human prostate cancer cells. Biomol. Ther. (Seoul) 20, 556-561. https://doi.org/10.4062/biomolther.2012.20.6.556
  18. Jia, Y., Zeng, Z. Z., Markwart, S. M., Rockwood, K. F., Ignatoski, K. M., Ethier, S. P. and Livant, D. L. (2004) Integrin fibronectin receptors in matrix metalloproteinase-1-dependent invasion by breast cancer and mammary epithelial cells. Cancer Res. 64, 8674-8681. https://doi.org/10.1158/0008-5472.CAN-04-0069
  19. Kim, C. W., Go, R. E. and Choi, K. C. (2015) Treatment of BG-1 ovarian cancer cells expressing estrogen receptors with lambdacyhalothrin and cypermethrin caused a partial estrogenicity via an estrogen receptor-dependent pathway. Toxicol. Res. 31, 331-337. https://doi.org/10.5487/TR.2015.31.4.331
  20. Lahlou, H. and Muller, W. J. (2011) ${\beta}1$-integrins signaling and mammary tumor progression in transgenic mouse models: implications for human breast cancer. Breast Cancer Res. 13, 229. https://doi.org/10.1186/bcr2905
  21. Lamb, L. E., Zarif, J. C. and Miranti, C. K. (2011) The androgen receptor induces integrin ${\alpha}6{\beta}1$ to promote prostate tumor cell survival via $NF-{\kappa}B$ and Bcl-xL Independently of PI3K signaling. Cancer Res. 71, 2739-2749. https://doi.org/10.1158/0008-5472.CAN-10-2745
  22. Lee, K. M., Ju, J. H., Jang, K., Yang, W., Yi, J. Y., Noh, D. Y. and Shin, I. (2012) CD24 regulates cell proliferation and transforming growth factor $\beta$-induced epithelial to mesenchymal transition through modulation of integrin ${\beta}1$ stability. Cell. Signal. 24, 2132-2142. https://doi.org/10.1016/j.cellsig.2012.07.005
  23. Lee, S. H., Yang, Y. J., Kim, K. M. and Chung, B. C. (2003) Altered urinary profiles of polyamines and endogenous steroids in patients with benign cervical disease and cervical cancer. Cancer Lett. 201, 121-131. https://doi.org/10.1016/S0304-3835(03)00014-4
  24. Liapis, H., Flath, A. and Kitazawa, S. (1996) Integrin ${\alpha}v{\beta}_3$ expression by bone-residing breast cancer metastases. Diagn. Mol. Pathol. 5, 127-135. https://doi.org/10.1097/00019606-199606000-00008
  25. Meng, X. N., Jin, Y., Yu, Y., Bai, J., Liu, G. Y., Zhu, J., Zhao, Y. Z., Wang, Z., Chen, F., Lee, K. Y. and Fu, S. B. (2009) Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration and invasion. Br. J. Cancer 101, 327-334. https://doi.org/10.1038/sj.bjc.6605154
  26. Miyoshi, Y., Ando, A., Hasegawa, S., Ishitobi, M., Taguchi, T., Tamaki, Y. and Noguchi, S. (2003) High expression of steroid sulfatase mRNA predicts poor prognosis in patients with estrogen receptor-positive breast cancer. Clin. Cancer Res. 9, 2288-2293.
  27. Monaghan, E., Gueorguiev, V., Wilkins-Port, C. and McKeown-Longo, P. J. (2004) The receptor for urokinase-type plasminogen activator regulates fibronectin matrix assembly in human skin fibroblasts. J. Biol. Chem. 279, 1400-1407. https://doi.org/10.1074/jbc.M310374200
  28. Morozevich, G., Kozlova, N., Cheglakov, I., Ushakova, N. and Berman, A. (2009) Integrin ${\alpha}5{\beta}1$ controls invasion of human breast carcinoma cells by direct and indirect modulation of MMP-2 collagenase activity. Cell Cycle 8, 2219-2225. https://doi.org/10.4161/cc.8.14.8980
  29. Muller, J. M., Krauss, B., Kaltschmidt, C., Baeuerle, P. A. and Rupec, R. A. (1997) Hypoxia induces c-fos transcription via a mitogen-activated protein kinase-dependent pathway. J. Biol. Chem. 272, 23435-23439. https://doi.org/10.1074/jbc.272.37.23435
  30. Nam, J. M., Onodera, Y., Bissell, M. J. and Park, C. C. (2010) Breast cancer cells in three-dimensional culture display an enhanced radioresponse after coordinate targeting of integrin ${\alpha}5{\beta}1$ and fibronectin. Cancer Res. 70, 5238-5248. https://doi.org/10.1158/0008-5472.CAN-09-2319
  31. Noh, H., Hong, S. and Huang, S. (2013) Role of urokinase receptor in tumor progression and development. Theranostics 3, 487-495. https://doi.org/10.7150/thno.4218
  32. Oloumi, A., McPhee, T. and Dedhar, S. (2004) Regulation of E-cadherin expression and $\beta$-catenin/Tcf transcriptional activity by the integrin-linked kinase. Biochim. Biophys. Acta 1691, 1-15. https://doi.org/10.1016/j.bbamcr.2003.12.002
  33. Pankov, R. and Yamada, K. M. (2002) Fibronectin at a glance. J. Cell Sci. 115, 3861-3863. https://doi.org/10.1242/jcs.00059
  34. Park, S. H., Cheung, L. W., Wong, A. S. and Leung, P. C. (2008) Estrogen regulates snail and slug in the down-regulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor $\alpha$. Mol. Endocrinol. 22, 2085-2098. https://doi.org/10.1210/me.2007-0512
  35. Purohit, A. and Foster, P. A. (2012) Steroid sulfatase inhibitors for estrogen- and androgen-dependent cancers. J. Endocrinol. 212, 99-110. https://doi.org/10.1530/JOE-11-0266
  36. Rasmussen, L. M., Zaveri, N. T., Stenvang, J., Peters, R. H. and Lykkesfeldt, A. E. (2007) A novel dual-target steroid sulfatase inhibitor and antiestrogen: SR 16157, a promising agent for the therapy of breast cancer. Breast Cancer Res. Treat. 106, 191-203. https://doi.org/10.1007/s10549-007-9494-y
  37. Rathinam, R. and Alahari, S. K. (2010) Important role of integrins in the cancer biology. Cancer Metastasis Rev. 29, 223-237. https://doi.org/10.1007/s10555-010-9211-x
  38. Rausch, L., Green, C., Steinmetz, K., LeValley, S., Catz, P., Zaveri, N., Schweikart, K., Tomaszewski, J. and Mirsalis, J. (2011) Preclinical pharmacokinetic, toxicological and biomarker evaluation of SR16157, a novel dual-acting steroid sulfatase inhibitor and selective estrogen receptor modulator. Cancer Chemother. Pharmacol. 67, 1341-1352. https://doi.org/10.1007/s00280-010-1430-x
  39. Reed, M. J., Purohit, A., Woo, L. W., Newman, S. P. and Potter, B. V. (2005) Steroid sulfatase: molecular biology, regulation, and inhibition. Endocr. Rev. 26, 171-202. https://doi.org/10.1210/er.2004-0003
  40. Rolli, M., Fransvea, E., Pilch, J., Saven, A. and Felding-Habermann, B. (2003) Activated integrin ${\alpha}v{\beta}3$ cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells. Proc. Natl . Acad. Sci. U.S.A. 100, 9482-9487. https://doi.org/10.1073/pnas.1633689100
  41. Sato, R., Suzuki, T., Katayose, Y., Miura, K., Shiiba, K., Tateno, H., Miki, Y., Akahira, J., Kamogawa, Y., Nagasaki, S., Yamamoto, K., Ii, T., Egawa, S., Evans, D. B., Unno, M. and Sasano, H. (2009) Steroid sulfatase and estrogen sulfotransferase in colon carcinoma: regulators of intratumoral estrogen concentrations and potent prognostic factors. Cancer Res. 69, 914-922. https://doi.org/10.1158/0008-5472.CAN-08-0906
  42. Schlaepfer, D. D., Hanks, S. K., Hunter, T. and van der Geer, P. (1994) Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature 372, 786-791. https://doi.org/10.1038/372786a0
  43. Schlaepfer, D. D. and Hunter, T. (1996) Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases. Mol. Cell. Biol. 16, 5623-5633. https://doi.org/10.1128/MCB.16.10.5623
  44. Sisci, D., Middea, E., Morelli, C., Lanzino, M., Aquila, S., Rizza, P., Catalano, S., Casaburi, I., Maggiolini, M. and Ando, S. (2010) $17{\beta}$-Estradiol enhances ${\alpha}5$ integrin subunit gene expression through $ER{\alpha}$-Sp1 interaction and reduces cell motility and invasion of $ER{\alpha}$-positive breast cancer cells. Breast Cancer Res. Treat. 124, 63-77. https://doi.org/10.1007/s10549-009-0713-6
  45. Suzuki, M., Ishida, H., Shiotsu, Y., Nakata, T., Akinaga, S., Takashima, S., Utsumi, T., Saeki, T. and Harada, N. (2009) Expression level of enzymes related to in situ estrogen synthesis and clinicopathological parameters in breast cancer patients. J. Steroid Biochem. Mol. Biol. 113, 195-201. https://doi.org/10.1016/j.jsbmb.2008.12.008
  46. Suzuki, T., Miki, Y., Nakamura, Y., Ito, K. and Sasano, H. (2011) Steroid sulfatase and estrogen sulfotransferase in human carcinomas. Mol. Cell. Endocrinol. 340, 148-153. https://doi.org/10.1016/j.mce.2010.11.001
  47. Utsumi, T., Yoshimura, N., Takeuchi, S., Maruta, M., Maeda, K. and Harada, N. (2000) Elevated steroid sulfatase expression in breast cancers. J. Steroid Biochem. Mol. Biol. 73, 141-145. https://doi.org/10.1016/S0960-0760(00)00060-1
  48. van der Flier, A. and Sonnenberg, A. (2001) Function and interactions of integrins. Cell Tissue Res. 305, 285-298. https://doi.org/10.1007/s004410100417
  49. Wang, J. G., Miyazu, M., Xiang, P., Li, S. N., Sokabe, M. and Naruse, K. (2005) Stretch-induced cell proliferation is mediated by FAK-MAPK pathway. Life Sci. 76, 2817-2825. https://doi.org/10.1016/j.lfs.2004.10.050
  50. Wilson, S. H., Ljubimov, A. V., Morla, A. O., Caballero, S., Shaw, L. C., Spoerri, P. E., Tarnuzzer, R. W. and Grant, M. B. (2003) Fibronectin fragments promote human retinal endothelial cell adhesion and proliferation and ERK activation through ${\alpha}5{\beta}1$ integrin and PI 3-kinase. Invest. Ophthalmol. Vis. Sci. 44, 1704-1715. https://doi.org/10.1167/iovs.02-0773
  51. Wood, P. M., Woo, L. W., Labrosse, J. R., Thomas, M. P., Mahon, M. F., Chander, S. K., Purohit, A., Reed, M. J. and Potter, B. V. (2010) Bicyclic derivatives of the potent dual aromatase-steroid sulfatase inhibitor 2-bromo-4-{[(4-cyanophenyl)(4h-1,2,4-triazol-4-yl)amino] methyl}phenylsulfamate: synthesis, SAR, crystal structure, and in vitro and in vivo activities. Chem. Med. Chem. 5, 1577-1593. https://doi.org/10.1002/cmdc.201000203
  52. Woodward, T. L., Mienaltowski, A. S., Modi, R. R., Bennett, J. M. and Haslam, S. Z. (2001) Fibronectin and the ${\alpha}5{\beta}1$ integrin are under developmental and ovarian steroid regulation in the normal mouse mammary gland. Endocrinology 142, 3214-3222. https://doi.org/10.1210/endo.142.7.8273
  53. Yamamoto, T., Kitawaki, J., Urabe, M., Honjo, H., Tamura, T., Noguchi, T., Okada, H., Sasaki, H., Tada, A., Terashima, Y., Nakamura, J. and Yoshihama, M. (1993) Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells. J. Steroid Biochem. Mol. Biol. 44, 463-468. https://doi.org/10.1016/0960-0760(93)90251-Q
  54. Yang, W., Zhang, Y., Li, Y., Wu, Z. and Zhu, D. (2007) Myostatin induces cyclin D1 degradation to cause cell cycle arrest through a phosphatidylinositol 3-kinase/AKT/GSK-3 $\beta$ pathway and is antagonized by insulin-like growth factor 1. J. Biol. Chem. 282, 3799-3808.

Cited by

  1. Understanding the pathophysiology of postpartum psychosis: Challenges and new approaches vol.7, pp.2, 2017, https://doi.org/10.5498/wjp.v7.i2.77
  2. Quantitative proteomic profiling of tumor-associated vascular endothelial cells in colorectal cancer vol.8, pp.5, 2017, https://doi.org/10.1242/bio.042838
  3. G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells vol.27, pp.6, 2017, https://doi.org/10.4062/biomolther.2019.063
  4. The Roles of Integrin α5β1 in Human Cancer vol.13, pp.None, 2017, https://doi.org/10.2147/ott.s273803
  5. Achieving the ratiometric imaging of steroid sulfatase in living cells and tissues with a two-photon fluorescent probe vol.56, pp.9, 2017, https://doi.org/10.1039/c9cc08672b
  6. Steroid sulfatase inhibitors: the current landscape vol.31, pp.6, 2017, https://doi.org/10.1080/13543776.2021.1910237