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Stephen P Ethier, PhD
Professor of Pathology & Laboratory Medicine
College of Medicine
MUSC

Email: ethier@musc.edu
 
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Stephen P Ethier, PhD

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Research Interest:

For many years, my laboratory has studied the mechanisms by which oncogenes transform human mammary epithelial cells and play a role in breast cancer development. My laboratory has a long standing interest in the mechanisms by which the HER-2 oncogene regulates the expression of transformed phenotypes in breast cancer cells. More recently, we have extended our focus to studies of the role of EGFR signaling in triple negative breast cancers, particularly those in which EGFR is activated via an autocrine loop involving one of its ligands, amphiregulin. Amphiregulin expression profoundly alters the biology of the EGF receptor in ways that result in the expression of a number of altered growth phenotypes. Over the past ten years, my team has developed a strong interest in breast cancer genomics. We have focused our efforts on understanding the oncogenes that are present on the 8p11 amplicon, which occurs in approximately 15% of human breast cancers and is exclusively seen in the most aggressive luminal B type breast cancers. WHSC1l1, DDHD2, and LSM1 are among the key oncogenes we have identified from these studies. Finally, we have recently incorporated the use of genome-scale shRNA screening strategies to identify other key breast cancer oncogenes that play important roles in breast cancer development and interact with other more well-known oncogenes to induce malignant transformation.

Honors:
Countess Alicia Spaulding-Paolozzi Distinguished Endowed Chair in Breast Cancer Diagnosis, Treatment, and Research

Positions:
Interim Director, Center for Genomic Medicine, Medical University of South Carolina
Leader, Cancer Genes & Molecular Regulation Program, Hollings Cancer Center, Medical University of South Carolina
Scientific Director, Genomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina

Selected Publications:

1.Findlay VJ, Wang C, Nogueira LM, Hurst K, Quirk D, Ethier SP, Staveley-O'Carroll KF, Watson DK, Camp ER. SNAI2 modulates colorectal cancer 5-fluorouracil sensitivity through miR145 repression. Mol Cancer Ther. ., 2014.
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2.Turner-Ivey B, Guest ST, Irish JC, Kappler CS, Garrett-Mayer E, Wilson RC, Ethier SP. KAT6A, a Chromatin Modifier from the 8p11-p12 Amplicon is a Candidate Oncogene in Luminal Breast Cancer. Neoplasia. .16(8):644-55, 2014.
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3.Timmerman LA, Holton T, Yuneva M, Louie RJ, Padró M, Daemen A, Hu M, Chan DA, Ethier SP, van 't Veer LJ, Polyak K, McCormick F, Gray JW. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. .24(4):450-65, 2013. PMCID: PMC3931310
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4.Holm K, Grabau D, Lövgren K, Aradottir S, Gruvberger-Saal S, Howlin J, Saal LH, Ethier SP, Bendahl PO, Stål O, Malmström P, Fernö M, Rydén L, Hegardt C, Borg Å, Ringnér M. Global H3K27 trimethylation and EZH2 abundance in breast tumor subtypes. Mol Oncol. .6(5):494-506, 2012.
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5.Wang G, Liu G, Wang X, Sethi S, Ali-Fehmi R, Abrams J, Zheng Z, Zhang K, Ethier S, Yang ZQ. ERLIN2 promotes breast cancer cell survival by modulating endoplasmic reticulum stress pathways. BMC Cancer. .12:225, 2012. PMCID: PMC3732090
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6.Piechocki MP, Wu GS, Jones RF, Jacob JB, Gibson H, Ethier SP, Abrams J, Yagita H, Venuprasad K, Wei WZ. Induction of proapoptotic antibodies to triple-negative breast cancer by vaccination with TRAIL death receptor DR5 DNA. Int J Cancer. .131(11):2562-72, 2012. PMCID: PMC3387508
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7.Baillo A, Giroux C, Ethier SP. Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast cancer. J Cell Physiol. .226(10):2691-701, 2011. PMCID: PMC3865809
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8.Fackler MJ, Umbricht CB, Williams D, Argani P, Cruz LA, Merino VF, Teo WW, Zhang Z, Huang P, Visvananthan K, Marks J, Ethier S, Gray JW, Wolff AC, Cope LM, Sukumar S. Genome-wide methylation analysis identifies genes specific to breast cancer hormone receptor status and risk of recurrence. Cancer Res. .71(19):6195-207, 2011. PMCID: PMC3308629
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9.Wu J, Liu S, Liu G, Dombkowski A, Abrams J, Martin-Trevino R, Wicha MS, Ethier SP, Yang ZQ. Identification and functional analysis of 9p24 amplified genes in human breast cancer. Oncogene. .31(3):333-41, 2011. PMCID: PMC3886828
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10.Bollig-Fischer A, Dewey TG, Ethier SP. Oncogene activation induces metabolic transformation resulting in insulin-independence in human breast cancer cells. PLoS One. .6(3):e17959, 2011. PMCID: PMC3060101
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11.Cote ML, Haddad R, Edwards DJ, Atikukke G, Gadgeel S, Soubani AO, Lonardo F, Bepler G, Schwartz AG, Ethier SP. Frequency and type of epidermal growth factor receptor mutations in African Americans with non-small cell lung cancer. J Thorac Oncol. .6(3):627-30, 2011. PMCID: PMC3057407
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12.Zhang H, Meng F, Liu G, Zhang B, Zhu J, Wu F, Ethier SP, Miller F, Wu G. Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis. Cancer Res. .71(4):1292-301, 2011. PMCID: PMC3906209
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13.Yang ZQ, Liu G, Bollig-Fischer A, Giroux CN, Ethier SP. Transforming properties of 8p11-12 amplified genes in human breast cancer. Cancer Res. .70(21):8487-97, 2010. PMCID: PMC3089754
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14.Bollig-Fischer A, Dziubinski M, Boyer A, Haddad R, Giroux CN, Ethier SP. HER-2 signaling, acquisition of growth factor independence, and regulation of biological networks associated with cell transformation. Cancer Res. .70(20):7862-73, 2010. PMCID: PMC3858175
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15.Mueller KL, Yang ZQ, Haddad R, Ethier SP, Boerner JL. EGFR/Met association regulates EGFR TKI resistance in breast cancer. J Mol Signal. .5:8, 2010. PMCID: PMC2911419
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16.Zhang H, Chen D, Ringler J, Chen W, Cui QC, Ethier SP, Dou QP, Wu G. Disulfiram treatment facilitates phosphoinositide 3-kinase inhibition in human breast cancer cells in vitro and in vivo. Cancer Res. .70(10):3996-4004, 2010. PMCID: PMC3827685
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17.Yang ZQ, Liu G, Bollig-Fischer A, Haddad R, Tarca AL, Ethier SP. Methylation-associated silencing of SFRP1 with an 8p11-12 amplification inhibits canonical and non-canonical WNT pathways in breast cancers. Int J Cancer. .125(7):1613-21, 2009. PMCID: PMC2735097
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18.Liu G, Bollig-Fischer A, Kreike B, van de Vijver MJ, Abrams J, Ethier SP, Yang ZQ. Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer. Oncogene. .28(50):4491-500, 2009. PMCID: PMC2795798
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19.Hollestelle A, Nagel JH, Smid M, Lam S, Elstrodt F, Wasielewski M, Ng SS, French PJ, Peeters JK, Rozendaal MJ, Riaz M, Koopman DG, Ten Hagen TL, de Leeuw BH, Zwarthoff EC, Teunisse A, van der Spek PJ, Klijn JG, Dinjens WN, Ethier SP, Clevers H, Jochemsen AG, den Bakker MA, Foekens JA, Martens JW, Schutte M. Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast Cancer Res Treat. .121(1):53-64, 2009.
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20.Arias-Romero LE, Saha S, Villamar-Cruz O, Yip SC, Ethier SP, Zhang ZY, Chernoff J. Activation of Src by protein tyrosine phosphatase 1B Is required for ErbB2 transformation of human breast epithelial cells. Cancer Res. .69(11):4582-8, 2009. PMCID: PMC2692630
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21.Lippman ME, Ethier S, Hayes DF. Editorial: Cost-effective analyses in Breast Cancer Research and Treatment [corrected]. Breast Cancer Res Treat. .115(2):221-2, 2009.
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22.Balan V, Nangia-Makker P, Schwartz AG, Jung YS, Tait L, Hogan V, Raz T, Wang Y, Yang ZQ, Wu GS, Guo Y, Li H, Abrams J, Couch FJ, Lingle WL, Lloyd RV, Ethier SP, Tainsky MA, Raz A. Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): a pilot study. Cancer Res. .68(24):10045-50, 2008. PMCID: PMC2882172
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23.Riggins RB, Lan JP, Zhu Y, Klimach U, Zwart A, Cavalli LR, Haddad BR, Chen L, Gong T, Xuan J, Ethier SP, Clarke R. ERRgamma mediates tamoxifen resistance in novel models of invasive lobular breast cancer. Cancer Res. .68(21):8908-17, 2008. PMCID: PMC2701641
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24.Willmarth NE, Baillo A, Dziubinski ML, Wilson K, Riese DJ, Ethier SP. Altered EGFR localization and degradation in human breast cancer cells with an amphiregulin/EGFR autocrine loop. Cell Signal. .21(2):212-9, 2008. PMCID: PMC2632975
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25.Mueller KL, Hunter LA, Ethier SP, Boerner JL. Met and c-Src cooperate to compensate for loss of epidermal growth factor receptor kinase activity in breast cancer cells. Cancer Res. .68(9):3314-22, 2008. PMCID: PMC3878202
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26.Willmarth NE, Ethier SP. Amphiregulin as a novel target for breast cancer therapy. J Mammary Gland Biol Neoplasia. .13(2):171-9, 2008.
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27.Wasielewski M, Hanifi-Moghaddam P, Hollestelle A, Merajver SD, van den Ouweland A, Klijn JG, Ethier SP, Schutte M. Deleterious CHEK2 1100delC and L303X mutants identified among 38 human breast cancer cell lines. Breast Cancer Res Treat. .113(2):285-91, 2008.
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28.Zhang H, Liu G, Dziubinski M, Yang Z, Ethier SP, Wu G. Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary epithelial cells. Breast Cancer Res Treat. .112(2):217-27, 2007.
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29.Saal LH, Gruvberger-Saal SK, Persson C, Lövgren K, Jumppanen M, Staaf J, Jönsson G, Pires MM, Maurer M, Holm K, Koujak S, Subramaniyam S, Vallon-Christersson J, Olsson H, Su T, Memeo L, Ludwig T, Ethier SP, Krogh M, Szabolcs M, Murty VV, Isola J, Hibshoosh H, Parsons R, Borg A. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet. .40(1):102-7, 2007. PMCID: PMC3018354
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30.Draghici S, Tarca AL, Yu L, Ethier S, Romero R. KUTE-BASE: storing, downloading and exporting MIAME-compliant microarray experiments in minutes rather than hours. Bioinformatics. .24(5):738-40, 2007. PMCID: PMC2386582
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31.Yang ZQ, Moffa AB, Haddad R, Streicher KL, Ethier SP. Transforming properties of TC-1 in human breast cancer: interaction with FGFR2 and beta-catenin signaling pathways. Int J Cancer. .121(6):1265-73, 2007.
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32.Streicher KL, Willmarth NE, Garcia J, Boerner JL, Dewey TG, Ethier SP. Activation of a nuclear factor kappaB/interleukin-1 positive feedback loop by amphiregulin in human breast cancer cells. Mol Cancer Res. .5(8):847-61, 2007.
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33.Diehl KM, Grewal N, Ethier SP, Woods-Ignatoski KM. p38MAPK-activated AKT in HER-2 overexpressing human breast cancer cells acts as an EGF-independent survival signal. J Surg Res. .142(1):162-9, 2007.
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34.Moffa AB, Ethier SP. Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells. J Cell Physiol. .210(3):720-31, 2007.
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35.Yang ZQ, Streicher KL, Ray ME, Abrams J, Ethier SP. Multiple interacting oncogenes on the 8p11-p12 amplicon in human breast cancer. Cancer Res. .66(24):11632-43, 2006.
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36.Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F, Speed T, Spellman PT, DeVries S, Lapuk A, Wang NJ, Kuo WL, Stilwell JL, Pinkel D, Albertson DG, Waldman FM, McCormick F, Dickson RB, Johnson MD, Lippman M, Ethier S, Gazdar A, Gray JW. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. .10(6):515-27, 2006. PMCID: PMC2730521
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37.Willmarth NE, Ethier SP. Autocrine and juxtacrine effects of amphiregulin on the proliferative, invasive, and migratory properties of normal and neoplastic human mammary epithelial cells. J Biol Chem. .281(49):37728-37, 2006.
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38.Streicher KL, Yang ZQ, Draghici S, Ethier SP. Transforming function of the LSM1 oncogene in human breast cancers with the 8p11-12 amplicon. Oncogene. .26(14):2104-14, 2006. PMCID: PMC2435249
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39.Hayes DF, Ethier S, Lippman ME. New guidelines for reporting of tumor marker studies in breast cancer research and treatment: REMARK. Breast Cancer Res Treat. .100(2):237-8, 2006.
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40.Pal M, Moffa A, Sreekumar A, Ethier SP, Barder TJ, Chinnaiyan A, Lubman DM. Differential phosphoprotein mapping in cancer cells using protein microarrays produced from 2-D liquid fractionation. Anal Chem. .78(3):702-10, 2006.
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41.Elstrodt F, Hollestelle A, Nagel JH, Gorin M, Wasielewski M, van den Ouweland A, Merajver SD, Ethier SP, Schutte M. BRCA1 mutation analysis of 41 human breast cancer cell lines reveals three new deleterious mutants. Cancer Res. .66(1):41-5, 2006.
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42.Gelsi-Boyer V, Orsetti B, Cervera N, Finetti P, Sircoulomb F, Rougé C, Lasorsa L, Letessier A, Ginestier C, Monville F, Esteyriès S, Adélaïde J, Esterni B, Henry C, Ethier SP, Bibeau F, Mozziconacci MJ, Charafe-Jauffret E, Jacquemier J, Bertucci F, Birnbaum D, Theillet C, Chaffanet M. Comprehensive profiling of 8p11-12 amplification in breast cancer. Mol Cancer Res. .3(12):655-67, 2005.
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43.Woods Ignatoski KM, Dziubinski ML, Ammerman C, Ethier SP. Cooperative interactions of HER-2 and HPV-16 oncoproteins in the malignant transformation of human mammary epithelial cells. Neoplasia. .7(8):788-98, 2005. PMCID: PMC1501888
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44.Berquin IM, Pang B, Dziubinski ML, Scott LM, Chen YQ, Nolan GP, Ethier SP. Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells. Oncogene. .24(19):3177-86, 2005.
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45.Jia Y, Zeng ZZ, Markwart SM, Rockwood KF, Ignatoski KM, Ethier SP, Livant DL. Integrin fibronectin receptors in matrix metalloproteinase-1-dependent invasion by breast cancer and mammary epithelial cells. Cancer Res. .64(23):8674-81, 2004.
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46.Moffa AB, Tannheimer SL, Ethier SP. Transforming potential of alternatively spliced variants of fibroblast growth factor receptor 2 in human mammary epithelial cells. Mol Cancer Res. .2(11):643-52, 2004.
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47.Yang ZQ, Albertson D, Ethier SP. Genomic organization of the 8p11-p12 amplicon in three breast cancer cell lines. Cancer Genet Cytogenet. .155(1):57-62, 2004.
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48.Rios-Doria J, Kuefer R, Ethier SP, Day ML. Cleavage of beta-catenin by calpain in prostate and mammary tumor cells. Cancer Res. .64(20):7237-40, 2004.
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49.Willmarth NE, Albertson DG, Ethier SP. Chromosomal instability and lack of cyclin E regulation in hCdc4 mutant human breast cancer cells. Breast Cancer Res. .6(5):R531-9, 2004. PMCID: PMC549168
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50.Song H, Ethier SP, Dziubinski ML, Lin J. Stat3 modulates heat shock 27kDa protein expression in breast epithelial cells. Biochem Biophys Res Commun. .314(1):143-50, 2004.
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51.Ray ME, Yang ZQ, Albertson D, Kleer CG, Washburn JG, Macoska JA, Ethier SP. Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer cell lines. Cancer Res. .64(1):40-7, 2004.
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52.Woods Ignatoski KM, Livant DL, Markwart S, Grewal NK, Ethier SP. The role of phosphatidylinositol 3'-kinase and its downstream signals in erbB-2-mediated transformation. Mol Cancer Res. .1(7):551-60, 2003.
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53.Woods Ignatoski KM, Grewal NK, Markwart S, Livant DL, Ethier SP. p38MAPK induces cell surface alpha4 integrin downregulation to facilitate erbB-2-mediated invasion. Neoplasia. .5(2):128-34, 2003. PMCID: PMC1550346
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54.Kumar-Sinha C, Ignatoski KW, Lippman ME, Ethier SP, Chinnaiyan AM. Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis. Cancer Res. .63(1):132-9, 2003.
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55.Popovici C, Basset C, Bertucci F, Orsetti B, Adélaide J, Mozziconacci MJ, Conte N, Murati A, Ginestier C, Charafe-Jauffret E, Ethier SP, Lafage-Pochitaloff M, Theillet C, Birnbaum D, Chaffanet M. Reciprocal translocations in breast tumor cell lines: cloning of a t(3;20) that targets the FHIT gene. Genes Chromosomes Cancer. .35(3):204-18, 2002.
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56.Billecke CA, Ljungman ME, McKay BC, Rehemtulla A, Taneja N, Ethier SP. Lack of functional pRb results in attenuated recovery of mRNA synthesis and increased apoptosis following UV radiation in human breast cancer cells. Oncogene. .21(29):4481-9, 2002.
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57.Ethier SP. Signal transduction pathways: the molecular basis for targeted therapies. Semin Radiat Oncol. .12(3 Suppl 2):3-10, 2002.
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58.Aprelikova O, Kuthiala A, Bessho M, Ethier S, Liu ET. BRCA1 protein level is not affected by peptide growth factors in MCF10A cell line. Oncogene. .13(11):2487-91, 1996.
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