Proteomic signatures of acquired letrozole resistance in breast cancer: Suppressed estrogen signaling and increased cell motility and invasiveness

Molecular and Cellular Proteomics

Volumn 12, Issue 9, 2013, Pages 2440-2455

  Tilghman, Syreeta L ^a,b   Townley, Ian ^b   Zhong, Qiu ^b   Carriere, Patrick P ^a   Zou, Jin ^b   Llopis, Shawn D ^a   Preyan, Lynez C ^a   Williams, Christopher C ^a   Skripnikova, Elena ^b   Bratton, Melyssa R ^b   Zhang, Qiang ^b   Wang, Guangdi ^a,b  

^a XAVIER UNIVERSITY OF LOUISIANA   (United States)

^b Cancer Research Program   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; AROMATASE; AROMATASE INHIBITOR; COMPLEMENTARY DNA; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN; ESTROGEN RECEPTOR ALPHA; FASCIN; INTEGRIN; LETROZOLE; MESSENGER RNA; PROTEIN; PROTEIN BCL 2; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; VIMENTIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOINFORMATICS; BREAST CANCER; CANCER CELL; CANCER SURVIVAL; CATION EXCHANGE; CELL MIGRATION; CELL STRAIN MCF 7; CONTROLLED STUDY; CYTOLYSIS; ENZYME INHIBITION; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; KAPLAN MEIER METHOD; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; NUDE MOUSE; OVARIECTOMY; PEPTIDE ANALYSIS; PHENOTYPE; POLYACRYLAMIDE GEL ELECTROPHORESIS; POSTMENOPAUSE; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; PROTEOMICS; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SOLID PHASE EXTRACTION; WESTERN BLOTTING;

ACTIN CYTOSKELETON; AMIDES; BLOTTING, WESTERN; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL MOVEMENT; CELL SHAPE; DRUG RESISTANCE, NEOPLASM; ESTROGENS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; KAPLAN-MEIER ESTIMATE; MESODERM; NEOPLASM INVASIVENESS; NEOPLASM PROTEINS; NITRILES; PROTEIN KINASE INHIBITORS; PROTEOMICS; PYRIDINES; RHO-ASSOCIATED KINASES; RHOA GTP-BINDING PROTEIN; SIGNAL TRANSDUCTION; TRIAZOLES; VIMENTIN;

EID: 84884381617     PISSN: 15359476     EISSN: 15359484     Source Type: Journal    
DOI: 10.1074/mcp.M112.023861     Document Type: Article

References (95)

1. Dunbier, A. K., Hong, Y., Masri, S., Brown, K. A., Sabnis, G. J., and Palomares, M. R. (2010) Progress in aromatase research and identification of key future directions. J Steroid Biochem. Mol. Biol 118, 311-315
2. Geisler, J., and Loønning, P. E. (2005) Aromatase inhibition: translation into a successful therapeutic approach. Clin. Cancer Res. 11, 2809-2821 (Pubitemid 40525179)
3. Sabnis, G., and Brodie, A. (2011) Adaptive changes results in activation of alternate signaling pathways and resistance to aromatase inhibitor resistance. Mol. Cell. Endocrinol. 340, 142-147
4. Dowsett, M., Martin, L. A., Smith, I., and Johnston, S. (2005) Mechanisms of resistance to aromatase inhibitors. J. Steroid Biochem. Mol. Biol. 95, 167-172 (Pubitemid 41137307)
5. Brodie, A., Macedo, L., and Sabnis, G. (2010) Aromatase resistance mechanisms in model systems in vivo. J. Steroid Biochem. Mol. Biol. 118, 283-287
6. Masri, S., Phung, S., Wang, X., and Chen, S. (2010) Molecular characterization of aromatase inhibitor-resistant, tamoxifen-resistant and LTEDaro cell lines. J. Steroid Biochem. Mol. Biol. 118, 277-282
7. Wong, C., and Chen, S. (2009) Heat shock protein 90 inhibitors: new mode of therapy to overcome endocrine resistance. Cancer Res. 69, 8670-8677
8. Masri, S., Phung, S., Wang, X., Wu, X., Yuan, Y. C., Wagman, L., and Chen, S. (2008) Genome-wide analysis of aromatase inhibitor-resistant, tamoxifen-resistant, and long-Term estrogen-deprived cells reveals a role for estrogen receptor. Cancer Res. 68, 4910-4918
9. Brodie, A., Sabnis, G., and Macedo, L. (2007) Xenograft models for aromatase inhibitor studies. J. Steroid Biochem. Mol. Biol. 106, 119-124 (Pubitemid 47362656)
10. Sabnis, G., and Brodie, A. (2010) Understanding resistance to endocrine agents: molecular mechanisms and potential for intervention. Clin. Breast Cancer 10, E6-E15
11. Chumsri, S., Sabnis, G. J., Howes, T., and Brodie, A. M. (2011) Aromatase inhibitors and xenograft studies. Steroids 76, 730-735
12. Jelovac, D., Sabnis, G., Long, B. J., Macedo, L., Goloubeva, O. G., and Brodie, A. M. (2005) Activation of mitogen-Activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole. Cancer Res. 65, 5380-5389 (Pubitemid 40834290)
13. Tilghman, S. L., Sabnis, G., and Brodie, A. M. (2011) Upregulation of AIB1, Aromatase and ER Provides Long-Term Estrogen Deprived Human Breast Cancer Cells with a Mechanistic Growth Advantage for Survival. Hormone Mol. Biol. Clin. Inv. 3, 357-366
14. Santner, S. J., Pauley, R. J., Tait, L., Kaseta, J., and Santen, R. J. (1997) Aromatase activity and expression in breast cancer and benign breast tissue stromal cells. J. Clin. Endocrinol. Metab. 82, 200-208 (Pubitemid 27021297)
15. Sutherland, R. M. (1988) Cell and environment interactions in tumor microregions: the multicell spheroid model. Science 240, 177-184
16. Sheikh, M. S., Shao, Z. M., Chen, J. C., and Fontana, J. A. (1993) Differential regulation of matrix Gla protein (MGP) gene expression by retinoic acid and estrogen in human breast carcinoma cells. Mol. Cell. Endocrinol. 92, 153-160 (Pubitemid 23124977)
17. Sun, X. Z., Zhou, D., and Chen, S. (1997) Autocrine and paracrine actions of breast tumor aromatase. A three-dimensional cell culture study involving aromatase transfected MCF-7 and T-47D cells. J. Steroid Biochem. Mol. Biol. 63, 29-36 (Pubitemid 28018134)
18. Silva, M. C., Rowlands, M. G., Dowsett, M., Gusterson, B., McKinna, J. A., Fryatt, I., and Coombes, R. C. (1989) Intratumoral aromatase as a prognostic factor in human breast carcinoma. Cancer Res. 49, 2588-2591 (Pubitemid 19143382)
19. Brodie, A., Lu, Q., and Nakamura, J. (1997) Aromatase in the normal breast and breast cancer. J. Steroid Biochem. Mol. Biol. 61, 281-286 (Pubitemid 27455690)
20. Bulun, S. E., and Simpson, E. R. (2008) Aromatase expression in women's cancers. Adv. Exp. Med. Biol. 630, 112-132
21. Bulun, S. E., Chen, D., Lu, M., Zhao, H., Cheng, Y., Demura, M., Yilmaz, B., Martin, R., Utsunomiya, H., Thung, S., Su, E., Marsh, E., Hakim, A., Yin, P., Ishikawa, H., Amin, S., Imir, G., Gurates, B., Attar, E., Reierstad, S., Innes, J., and Lin, Z. (2007) Aromatase excess in cancers of breast, endometrium and ovary. J. Steroid Biochem. Mol. Biol. 106, 81-96 (Pubitemid 47362640)
22. Long, B. J., Jelovac, D., Thiantanawat, A., and Brodie, A. M. (2002) The effect of second-line antiestrogen therapy on breast tumor growth after first-line treatment with the aromatase inhibitor letrozole: long-Term studies using the intratumoral aromatase postmenopausal breast cancer model. Clin. Cancer Res. 8, 2378-2388 (Pubitemid 34753613)
23. Brodie, A., Jelovac, D., Sabnis, G., Long, B., Macedo, L., and Goloubeva, O. (2005) Model systems: mechanisms involved in the loss of sensitivity to letrozole. J. Steroid Biochem. Mol. Biol. 95, 41-48 (Pubitemid 41137292)
24. Pfaffl, M. W., Lange, I. G., Daxenberger, A., and Meyer, H. H. (2001) Tissue-specific expression pattern of estrogen receptors (ER): quantification of ER alpha and ER beta mRNA with real-Time RT-PCR. APMIS 109, 345-355 (Pubitemid 32640882)
25. Guo, Y., Singleton, P. A., Rowshan, A., Gucek, M., Cole, R. N., Graham, D. R., Van Eyk, J. E., and Garcia, J. G. (2007) Quantitative proteomics analysis of human endothelial cell membrane rafts: evidence of MARCKS and MRP regulation in the sphingosine 1-phosphate-induced barrier enhancement. Mol. Cell. Proteomics 6, 689-696 (Pubitemid 46630101)
26. Pierce, A., Unwin, R. D., Evans, C. A., Griffiths, S., Carney, L., Zhang, L., Jaworska, E., Lee, C. F., Blinco, D., Okoniewski, M. J., Miller, C. J., Bitton, D. A., Spooncer, E., and Whetton, A. D. (2008) Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases. Mol. Cell. Proteomics 7, 853-863 (Pubitemid 351737087)
27. Tan, H. T., Tan, S., Lin, Q., Lim, T. K., Hew, C. L., and Chung, M. C. (2008) Quantitative and temporal proteome analysis of butyrate-Treated colorectal cancer cells. Mol. Cell. Proteomics 7, 1174-1185 (Pubitemid 351943963)
28. Thomas, P. D., Campbell, M. J., Kejariwal, A., Mi, H., Karlak, B., Daverman, R., Diemer, K., Muruganujan, A., and Narechania, A. (2003) PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 13, 2129-2141 (Pubitemid 37161770)
29. van Iersel, M. P., Kelder, T., Pico, A. R., Hanspers, K., Coort, S., Conklin, B. R., and Evelo, C. (2008) Presenting and exploring biological pathways with PathVisio. BMC Bioinformatics 9, 399
30. Pico, A. R., Kelder, T., van Iersel, M. P., Hanspers, K., Conklin, B. R., and Evelo, C. (2008) WikiPathways: pathway editing for the people. PLoS Biol. 6, e184
31. Kanehisa, M., Goto, S., Hattori, M., Aoki-Kinoshita, K. F., Itoh, M., Kawashima, S., Katayama, T., Araki, M., and Hirakawa, M. (2006) From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res. 34, D354-D357
32. Kanehisa, M., and Goto, S. (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27-30 (Pubitemid 30047706)
33. Kanehisa, M., Goto, S., Furumichi, M., Tanabe, M., and Hirakawa, M. (2010) KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 38, D355-D360
34. Györffy, B., Lanczky, A., Eklund, A. C., Denkert, C., Budczies, J., Li, Q., and Szallasi, Z. (2010) An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res. Treat. 123, 725-731
35. Bretschneider, N., Kangaspeska, S., Seifert, M., Reid, G., Gannon, F., and Denger, S. (2008) E2-mediated cathepsin D (CTSD) activation involves looping of distal enhancer elements. Mol. Oncol. 2, 182-190
36. Markićević, M., Petrović, A., Kanjer, K., Nesković-Konstantinović, Z., and Nikolić- Vukosavujević, D. (2008) Estrogen-regulated cut-off values of pS2 and cathepsin D expression in breast carcinomas. Adv. Exp. Med. Biol. 617, 341-348
37. Kristek, J., Dmitrović, B., Kurbel, S., Sakić, K., Krajinović, Z., Blazicević, V., Has, B., and Marjanović, K. (2007) Tumor growth fraction, expression of estrogen and progesterone receptors, p53, bcl-2 and cathepsin D activity in primary ductal invasive breast carcinoma and their axillary lymph node metastases. Coll. Antropol. 31, 1043-1047
38. Dunbier, A. K., Anderson, H., Ghazoui, Z., Folkerd, E. J., A'Hern, R., Crowder, R. J., Hoog, J., Smith, I. E., Osin, P., Nerurkar, A., Parker, J. S., Perou, C. M., Ellis, M. J., and Dowsett, M. (2010) Relationship between plasma estradiol levels and estrogen-responsive gene expression in estrogen receptor-positive breast cancer in postmenopausal women. J. Clin. Oncol. 28, 1161-1167
39. Corte, M. D., Tamargo, F., Alvarez, A., Rodriguez, J. C., Vázquez, J., Sánchez, R., Lamelas, M. L., González, L. O., Allende, M. T., Garcia-Muñiz, J. L., Fueyo, A., and Vizoso, F. (2006) Cytosolic levels of TFF1/pS2 in breast cancer: Their relationship with clinical-pathological parameters and their prognostic significance. Breast Cancer Res. Treat. 96, 63-72
40. Ioachim, E., Tsanou, E., Briasoulis, E., Batsis, Ch, Karavasilis, V., Charchanti, A., Pavlidis, N., and Agnantis, N. J. (2003) Clinicopathological study of the expression of hsp27, pS2, cathepsin D and metallothionein in primary invasive breast cancer. Breast 12, 111-119 (Pubitemid 36546435)
41. Itoh, T., Karlsberg, K., Kijima, I., Yuan, Y. C., Smith, D., Ye, J., and Chen, S. (2005) Letrozole-, anastrozole-, and tamoxifen-responsive genes in MCF-7aro cells: a microarray approach. Mol. Cancer Res. 3, 203-218 (Pubitemid 40525331)
42. Yang, J., Jubb, A. M., Pike, L., Buffa, F. M., Turley, H., Baban, D., Leek, R., Gatter, K. C., Ragoussis, J., and Harris, A. L. (2010) The histone demethylase JMJD2B is regulated by estrogen receptor alpha and hypoxia, and is a key mediator of estrogen induced growth. Cancer Res. 70, 6456-6466
43. Divekar, S. D., Storchan, G. B., Sperle, K., Veselik, D. J., Johnson, E., Dakshanamurthy, S., Lajiminmuhip, Y. N., Nakles, R. E., Huang, L., and Martin, M. B. (2011) The role of calcium in the activation of estrogen receptor-Alpha. Cancer Res. 71, 1658-1668
44. Symmans, W. F., Fiterman, D. J., Anderson, S. K., Ayers, M., Rouzier, R., Dunmire, V., Stec, J., Valero, V., Sneige, N., Albarracin, C., Wu, Y., Ross, J. S., Wagner, P., Theriault, R. L., Arun, B., Kuerer, H., Hess, K. R., Zhang, W., Hortobagyi, G. N., and Pusztai, L. (2005) A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding. Endocr. Relat. Cancer 12, 1059-1069 (Pubitemid 41815797)
45. Cascio, S., Zhang, L., and Finn, O. J. (2011) MUC1 protein expression in tumor cells regulates transcription of proinflammatory cytokines by forming a complex with nuclear factor-kappaB p65 and binding to cytokine promoters: importance of extracellular domain. J. Biol. Chem. 286, 42248-42256
46. Backus, J., Laughlin, T., Wang, Y., Belly, R., White, R., Baden, J., Justus Min, C., Mannie, A., Tafra, L., Atkins, D., and Verbanac, K. M. (2005) Identification and characterization of optimal gene expression markers for detection of breast cancer metastasis. J. Mol. Diagn. 7, 327-336 (Pubitemid 41149647)
47. Viana Lde, S., Affonso, R. J., Jr., Silva, S. R., Denadai, M. V., Matos, D., Salinas de Souza, C., and Waisberg, J. (2013) Relationship between the Expression of the Extracellular Matrix Genes SPARC, SPP1, FN1, ITGA5 and ITGAV and Clinicopathological Parameters of Tumor Progression and Colorectal Cancer Dissemination. Oncology 84, 81-91
48. Francois, P., Bertos, N., Laferrière, J., Sadekova, S., Souleimanova, M., Zhao, H., Finak, G., Meterissian, S., Hallett, M. T., and Park, M. (2012) Gene-expression profiling of microdissected breast cancer microvasculature identifies distinct tumor vascular subtypes. Breast Cancer Res. 14, R120
49. Lu, J. G., Li, Y., Li, L., and Kan, X. (2011) Overexpression of osteopontin and integrin alphav in laryngeal and hypopharyngeal carcinomas associated with differentiation and metastasis. J. Cancer Res. Clin. Oncol. 137, 1613-1618
50. Nejjari, M., Hafdi, Z., Gouysse, G., Fiorentino, M., Béatrix, O., Dumortier, J., Pourreyron, C., Barozzi, C., D'Errico, A., Grigioni, W. F., and Scoazec, J. Y. (2002) Expression, regulation, and function of alpha V integrins in hepatocellular carcinoma: an in vivo and in vitro study. Hepatology 36, 418-426 (Pubitemid 34810362)
51. Wong, N. C., Mueller, B. M., Barbas, C. F., Ruminski, P., Quaranta, V., Lin, E. C., and Smith, J. W. (1998) Alphav integrins mediate adhesion and migration of breast carcinoma cell lines. Clin. Exp. Metastasis 16, 50-61 (Pubitemid 28122555)
52. Chen, L., Yang, S., Jakoncic, J., Zhang, J. J., and Huang, X. Y. (2010) Migrastatin analogues target fascin to block tumour metastasis. Nature 464, 1062-1066
53. Hashimoto, Y., Kim, D. J., and Adams, J. C. (2011) The roles of fascins in health and disease. J. Pathol. 224, 289-300
54. Jayo, A., and Parsons, M. (2010) Fascin: a key regulator of cytoskeletal dynamics. Int. J. Biochem. Cell Biol. 42, 1614-1617
55. Al-Alwan, M., Olabi, S., Ghebeh, H., Barhoush, E., Tulbah, A., Al-Tweigeri, T., Ajarim, D., and Adra, C. (2011) Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-Associated molecules. PLoS One 6, e27339
56. Vega, F. M., Fruhwirth, G., Ng, T., and Ridley, A. J. (2011) RhoA and RhoC have distinct roles in migration and invasion by acting through different targets. J. Cell Biol. 193, 655-665
57. Carreira, S., Goodall, J., Denat, L., Rodriguez, M., Nuciforo, P., Hoek, K. S., Testori, A., Larue, L., and Goding, C. R. (2006) Mitf regulation of Dia1 controls melanoma proliferation and invasiveness. Genes Dev. 20, 3426-3439 (Pubitemid 44969160)
58. Hirata, H., Tatsumi, H., and Sokabe, M. (2008) Mechanical forces facilitate actin polymerization at focal adhesions in a zyxin-dependent manner. J. Cell Sci. 121, 2795-2804
59. Vignjevic, D., Kojima, S., Aratyn, Y., Danciu, O., Svitkina, T., and Borisy, G. G. (2006) Role of fascin in filopodial protrusion. J. Cell Biol. 174, 863-875 (Pubitemid 44373735)
60. Miller, T. W., Balko, J. M., Ghazoui, Z., Dunbier, A., Anderson, H., Dowsett, M., Gonzalez-Angulo, A. M., Mills, G. B., Miller, W. R., Wu, H., Shyr, Y., and Arteaga, C. L. (2011) A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance. Clin. Cancer Res. 17, 2024-2034
61. Chen, S. (2011) An "omics" approach to determine the mechanisms of acquired aromatase inhibitor resistance. OMICS 15, 347-352
62. McLeskey, S. W., Zhang, L., El-Ashry, D., Trock, B. J., Lopez, C. A., Kharbanda, S., Tobias, C. A., Lorant, L. A., Hannum, R. S., Dickson, R. B., and Kern, F. G. (1998) Tamoxifen-resistant fibroblast growth factor-Transfected MCF-7 cells are cross-resistant in vivo to the antiestrogen ICI 182,780 and two aromatase inhibitors. Clin. Cancer Res. 4, 697-711 (Pubitemid 28193571)
63. Miller, W. R., Anderson, T. J., White, S., Evans, D., Krause, A., and Dixon, J. M. (2005) Growth factor signalling in clinical breast cancer and its impact on response to conventional therapies: the Edinburgh experience. Endocr. Relat. Cancer 12, S119-S123 (Pubitemid 41395419)
64. Ellis, M. J., Tao, Y., Young, O., White, S., Proia, A. D., Murray, J., Renshaw, L., Faratian, D., Thomas, J., Dowsett, M., Krause, A., Evans, D. B., Miller, W. R., and Dixon, J. M. (2006) Estrogen-independent proliferation is present in estrogen-receptor HER2-positive primary breast cancer after neoadjuvant letrozole. J. Clin. Oncol. 24, 3019-3025 (Pubitemid 46638935)
65. Zhang, G. J., Kimijima, I., Tsuchiya, A., and Abe, R. (1998) The role of bcl-2 expression in breast carcinomas (Review). Oncol. Rep. 5, 1211-1216 (Pubitemid 28372589)
66. Lee, K. H., Im, S. A., Oh, D. Y., Lee, S. H., Chie, E. K., Han, W., Kim, D. W., Kim, T. Y., Park, I. A., Noh, D. Y., Heo, D. S., Ha, S. W., and Bang, Y. J. (2007) Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy. BMC Cancer 7, 63
67. Nadler, Y., Camp, R. L., Giltnane, J. M., Moeder, C., Rimm, D. L., Kluger, H. M., and Kluger, Y. (2008) Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Res. 10, R35
68. Tawfik, K., Kimler, B. F., Davis, M. K., Fan, F., and Tawfik, O. (2012) Prognostic significance of Bcl-2 in invasive mammary carcinomas: a comparative clinicopathologic study between "triple-negative" and non-"triple-negative" tumors. Hum. Pathol. 43, 23-30
69. Arumugam, T., Simeone, D. M., Van Golen, K., and Logsdon, C. D. (2005) S100P promotes pancreatic cancer growth, survival, and invasion. Clin. Cancer Res. 11, 5356-5364 (Pubitemid 41060808)
70. Fuentes, M. K., Nigavekar, S. S., Arumugam, T., Logsdon, C. D., Schmidt, A. M., Park, J. C., and Huang, E. H. (2007) RAGE activation by S100P in colon cancer stimulates growth, migration, and cell signaling pathways. Dis. Colon Rectum. 50, 1230-1240 (Pubitemid 47087458)
71. Arumugam, T., Simeone, D. M., Schmidt, A. M., and Logsdon, C. D. (2004) S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J. Biol. Chem. 279, 5059-5065 (Pubitemid 38220521)
72. Yamamoto, T., Gotoh, M., Kitajima, M., and Hirohashi, S. (1993) Thymosin beta-4 expression is correlated with metastatic capacity of colorectal carcinomas. Biochem. Biophys. Res. Commun. 193, 706-710 (Pubitemid 23214285)
73. Kobayashi, T., Okada, F., Fujii, N., Tomita, N., Ito, S., Tazawa, H., Aoyama, T., Choi, S. K., Shibata, T., Fujita, H., and Hosokawa, M. (2002) Thymosin-beta4 regulates motility and metastasis of malignant mouse fibrosarcoma cells. Am. J. Pathol. 160, 869-882 (Pubitemid 34224577)
74. Wang, W. S., Chen, P. M., Hsiao, H. L., Ju, S. Y., and Su, Y. (2003) Overexpression of the thymosin beta-4 gene is associated with malignant progression of SW480 colon cancer cells. Oncogene 22, 3297-3306 (Pubitemid 36712942)
75. Xu, Y. F., Yu, S. N., Lu, Z. H., Liu, J. P., and Chen, J. (2011) Fascin promotes the motility and invasiveness of pancreatic cancer cells. World J. Gastroenterol. 17, 4470-4478
76. Snyder, M., Huang, X. Y., and Zhang, J. J. (2011) Signal transducers and activators of transcription 3 (STAT3) directly regulates cytokine-induced fascin expression and is required for breast cancer cell migration. J. Biol. Chem. 286, 38886-38893
77. Darnel, A. D., Behmoaram, E., Vollmer, R. T., Corcos, J., Bijian, K., Sircar, K., Su, J., Jiao, J., Alaoui-Jamali, M. A., and Bismar, T. A. (2009) Fascin regulates prostate cancer cell invasion and is associated with metastasis and biochemical failure in prostate cancer. Clin. Cancer Res. 15, 1376-1383
78. Hashimoto, Y., Ito, T., Inoue, H., Okumura, T., Tanaka, E., Tsunoda, S., Higashiyama, M., Watanabe, G., Imamura, M., and Shimada, Y. (2005) Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma. Clin. Cancer Res. 11, 2597-2605 (Pubitemid 40569459)
79. Yoder, B. J., Tso, E., Skacel, M., Pettay, J., Tarr, S., Budd, T., Tubbs, R. R., Adams, J. C., and Hicks, D. G. (2005) The expression of fascin, an actin-bundling motility protein, correlates with hormone receptor-negative breast cancer and a more aggressive clinical course. Clin. Cancer Res. 11, 186-192 (Pubitemid 40075794)
80. Radel, C., and Rizzo, V. (2005) Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization. Am. J. Physiol. Heart Circ. Physiol. 288, H936-H945 (Pubitemid 40139682)
81. Grande-Garcia, A., Echarri, A., de Rooij, J., Alderson, N. B., Waterman-Storer, C. M., Valdivielso, J. M., and del Pozo, M. A. (2007) Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases. J. Cell Biol. 177, 683-694 (Pubitemid 46799839)
82. Joshi, B., Strugnell, S. S., Goetz, J. G., Kojic, L. D., Cox, M. E., Griffith, O. L., Chan, S. K., Jones, S. J., Leung, S. P., Masoudi, H., Leung, S., Wiseman, S. M., and Nabi, I. R. (2008) Phosphorylated caveolin-1 regulates Rho/ROCK-dependent focal adhesion dynamics and tumor cell migration and invasion. Cancer Res. 68, 8210-8220
83. Pinilla, S. M., Honrado, E., Hardisson, D., Benitez, J., and Palacios, J. (2006) Caveolin-1 expression is associated with a basal-like phenotype in sporadic and hereditary breast cancer. Breast Cancer Res. Treat 99, 85-90 (Pubitemid 44168607)
84. Savage, K., Lambros, M. B., Robertson, D., Jones, R. L., Jones, C., Mackay, A., James, M., Hornick, J. L., Pereira, E. M., Milanezi, F., Fletcher, C. D., Schmitt, F. C., Ashworth, A., and Reis-Filho, J. S. (2007) Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clin. Cancer Res. 13, 90-101 (Pubitemid 46121857)
85. Brandt, D. T., Baarlink, C., Kitzing, T. M., Kremmer, E., Ivaska, J., Nollau, P., and Grosse, R. (2009) SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin. Nat. Cell Biol. 11, 557-568
86. Li, J., Tu, Y., Wen, J., Yao, F., Wei, W., and Sun, S. (2010) Role for ezrin in breast cancer cell chemotaxis to CCL5. Oncol. Rep. 24, 965-971
87. Sahai, E., and Marshall, C. J. (2003) Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nat. Cell Biol. 5, 711-719 (Pubitemid 36986778)
88. Bartkowiak, K., Wieczorek, M., Buck, F., Harder, S., Moldenhauer, J., Effenberger, K. E., Pantel, K., Peter-Katalinic, J., and Brandt, B. H. (2009) Two-dimensional differential gel electrophoresis of a cell line derived from a breast cancer micrometastasis revealed a stem/progenitor cell protein profile. J. Proteome Res. 8, 2004-2014
89. Austermann, J., Nazmi, A. R., Muller-Tidow, C., and Gerke, V. (2008) Characterization of the Ca2-regulated ezrin-S100P interaction and its role in tumor cell migration. J. Biol. Chem. 283, 29331-29340
90. Taube, J. H., Herschkowitz, J. I., Komurov, K., Zhou, A. Y., Gupta, S., Yang, J., Hartwell, K., Onder, T. T., Gupta, P. B., Evans, K. W., Hollier, B. G., Ram, P. T., Lander, E. S., Rosen, J. M., Weinberg, R. A., and Mani, S. A. (2010) 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. 107, 15449-15454
91. Sarrio, D., Rodriguez-Pinilla, S. M., Hardisson, D., Cano, A., Moreno-Bueno, G., and Palacios, J. (2008) Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res. 68, 989-997 (Pubitemid 351272216)
92. May, C. D., Sphyris, N., Evans, K. W., Werden, S. J., Guo, W., and Mani, S. A. (2011) Epithelial-mesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression. Breast Cancer Res. 13, 202
93. Creighton, C. J., Li, X., Landis, M., Dixon, J. M., Neumeister, V. M., Sjolund, A., Rimm, D. L., Wong, H., Rodriguez, A., Herschkowitz, J. I., Fan, C., Zhang, X., He, X., Pavlick, A., Gutierrez, M. C., Renshaw, L., Larionov, A. A., Faratian, D., Hilsenbeck, S. G., Perou, C. M., Lewis, M. T., Rosen, J. M., and Chang, J. C. (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc. Natl. Acad. Sci. U.S.A. 106, 13820-13825
94. Huang, H. C., Hu, C. H., Tang, M. C., Wang, W. S., Chen, P. M., and Su, Y. (2007) Thymosin beta4 triggers an epithelial-mesenchymal transition in colorectal carcinoma by upregulating integrin-linked kinase. Oncogene 26, 2781-2790 (Pubitemid 46663833)
95. Gupta, A., Mehta, R., Alimirah, F., Peng, X., Murillo, G., Wiehle, R., Mehta, R. G. (2013) Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells. J. Steroid Biochem. Mol. Biol. 133, 30-42