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36 results on '"Shah, Esha T."'

1. Inhibition of Aurora B kinase (AURKB) enhances the effectiveness of 5-fluorouracil chemotherapy against colorectal cancer cells

Author

Shah, Esha T., Molloy, Christopher, Gough, Madeline, Kryza, Thomas, Samuel, Selwin G., Tucker, Amos, Bhatia, Maneet, Ferguson, Genevieve, Heyman, Rebecca, Vora, Shivam, Monkman, James, Bolderson, Emma, Kulasinghe, Arutha, He, Yaowu, Gabrielli, Brian, Hooper, John D., Richard, Derek J., O’Byrne, Kenneth J., and Adams, Mark N.

Published
2024
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9. hSSB1 (NABP2/OBFC2B) modulates the DNA damage and androgen‐induced transcriptional response in prostate cancer

Author

Adams, Mark N., primary, Croft, Laura V., additional, Urquhart, Aaron, additional, Saleem, Mohamed Ashick Mohamed, additional, Rockstroh, Anja, additional, Duijf, Pascal H. G., additional, Thomas, Patrick B., additional, Ferguson, Genevieve P., additional, Najib, Idris Mohd, additional, Shah, Esha T., additional, Bolderson, Emma, additional, Nagaraj, Shivashankar, additional, Williams, Elizabeth D., additional, Nelson, Colleen C., additional, O'Byrne, Kenneth J., additional, and Richard, Derek J., additional

Published
2023
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10. Spatial Profiling Identifies Prognostic Features of Response to Adjuvant Therapy in Triple Negative Breast Cancer (TNBC)

Author

Kulasinghe, Arutha, Monkman, James, Shah, Esha T., Matigian, Nicholas, Adams, Mark N., O’Byrne, Ken, Kulasinghe, Arutha, Monkman, James, Shah, Esha T., Matigian, Nicholas, Adams, Mark N., and O’Byrne, Ken

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has few effective treatment options due to its lack of targetable hormone receptors. Whilst the degree of tumour infiltrating lymphocytes (TILs) has been shown to associate with therapy response and prognosis, deeper characterization of the molecular diversity that may mediate chemotherapeutic response is lacking. Here we applied targeted proteomic analysis of both chemotherapy sensitive and resistant TNBC tissue samples by the Nanostring GeoMx Digital Spatial Platform (DSP). By quantifying 68 targets in the tumour and tumour microenvironment (TME) compartments and performing differential expression analysis between responsive and non-responsive tumours, we show that increased ER-alpha expression and decreased 4-1BB and MART1 within the stromal compartments is associated with adjuvant chemotherapy response. Similarly, higher expression of GZMA, STING and fibronectin and lower levels of CD80 were associated with response within tumour compartments. Univariate overall-survival (OS) analysis of stromal proteins supported these findings, with ER-alpha expression (HR=0.19, p=0.0012) associated with better OS while MART1 expression (HR=2.3, p=0.035) was indicative of poorer OS. Proteins within tumour compartments consistent with longer OS included PD-L1 (HR=0.53, p=0.023), FOXP3 (HR=0.5, p=0.026), GITR (HR=0.51, p=0.036), SMA (HR=0.59, p=0.043), while EPCAM (HR=1.7, p=0.045), and CD95 (HR=4.9, p=0.046) expression were associated with shorter OS. Our data provides early insights into the levels of these markers in the TNBC tumour microenvironment, and their association with chemotherapeutic response and patient survival.

Published
2022

12. Elevating CDCA3 Levels Enhances Tyrosine Kinase Inhibitor Sensitivity in TKI-Resistant EGFR Mutant Non-Small-Cell Lung Cancer

Author

Sahin, Katherine B., primary, Shah, Esha T., additional, Ferguson, Genevieve P., additional, Molloy, Christopher, additional, Kalita-de Croft, Priyakshi, additional, Hayes, Sarah A., additional, Hudson, Amanda, additional, Colvin, Emily, additional, Kamitakahara, Hannah, additional, Harvie, Rozelle, additional, Hasovits, Csilla, additional, Khan, Tashbib, additional, Duijf, Pascal H. G., additional, Howell, Viive M., additional, He, Yaowu, additional, Bolderson, Emma, additional, Hooper, John D., additional, Lakhani, Sunil R., additional, Richard, Derek J., additional, O’Byrne, Kenneth J., additional, and Adams, Mark N., additional

Published
2021
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13. Elevating CDCA3 levels enhances tyrosine kinase inhibitor sensitivity in TKI-resistant EGFR mutant non-small-cell lung cancer

Author

Sahin, Katherine B., Shah, Esha T., Ferguson, Genevieve P., Molloy, Christopher, Kalita-De Croft, Priyakshi, Hayes, Sarah A., Hudson, Amanda, Colvin, Emily, Kamitakahara, Hannah, Harvie, Rozelle, Hasovits, Csilla, Khan, Tashbib, Duijf, Pascal H.G., Howell, Viive M., He, Yaowu, Bolderson, Emma, Hooper, John D., Lakhani, Sunil R., Richard, Derek J., O’byrne, Kenneth J., Adams, Mark N., Sahin, Katherine B., Shah, Esha T., Ferguson, Genevieve P., Molloy, Christopher, Kalita-De Croft, Priyakshi, Hayes, Sarah A., Hudson, Amanda, Colvin, Emily, Kamitakahara, Hannah, Harvie, Rozelle, Hasovits, Csilla, Khan, Tashbib, Duijf, Pascal H.G., Howell, Viive M., He, Yaowu, Bolderson, Emma, Hooper, John D., Lakhani, Sunil R., Richard, Derek J., O’byrne, Kenneth J., and Adams, Mark N.

Abstract

Tyrosine kinase inhibitors (TKIs) are the first-line therapy for non-small-cell lung cancers (NSCLC) that harbour sensitising mutations within the epidermal growth factor receptor (EGFR). However, resistance remains a key issue, with tumour relapse likely to occur. We have previously identified that cell division cycle-associated protein 3 (CDCA3) is elevated in adenocarcinoma (LUAD) and correlates with sensitivity to platinum-based chemotherapy. Herein, we explored whether CDCA3 levels were associated with EGFR mutant LUAD and TKI response. We demonstrate that in a small-cohort tissue microarray and in vitro LUAD cell line panel, CDCA3 protein levels are elevated in EGFR mutant NSCLC as a result of increased protein stability downstream of receptor tyrosine kinase signalling. Here, CDCA3 protein levels correlated with TKI potency, whereby CDCA3high EGFR mutant NSCLC cells were most sensitive. Consistently, ectopic overexpression or inhibition of casein kinase 2 using CX-4945, which pharmacologically prevents CDCA3 degradation, upregulated CDCA3 levels and the response of T790M(+) H1975 cells and two models of acquired resistance to TKIs. Accordingly, it is possible that strategies to upregulate CDCA3 levels, particularly in CDCA3low tumours or upon the emergence of therapy resistance, might improve the response to EGFR TKIs and benefit patients.

Published
2021

14. Identification of Proteins Deregulated by Platinum-Based Chemotherapy as Novel Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer

Author

Ryan, Sarah-Louise, primary, Dave, Keyur A., additional, Beard, Sam, additional, Gyimesi, Martina, additional, McTaggart, Matthew, additional, Sahin, Katherine B., additional, Molloy, Christopher, additional, Gandhi, Neha S., additional, Boittier, Eric, additional, O’Leary, Connor G., additional, Shah, Esha T., additional, Bolderson, Emma, additional, Baird, Anne-Marie, additional, Richard, Derek J., additional, O’Byrne, Kenneth J., additional, and Adams, Mark N., additional

Published
2021
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17. The long non-coding RNA GHSROS facilitates breast cancer cell migration and orthotopic xenograft tumour growth

Author

Thomas, Patrick B., Seim, Inge, Jeffery, Penny L., Gahete, Manuel D., Maugham, Michelle, Crisp, Gabrielle J., Stacey, Andrew, Shah, Esha T., Walpole, Carina, Whiteside, Eliza J., Nelson, Colleen C., Herington, Adrian C., Luque, Raúl M., Veedu, Rakesh N., Chopin, Lisa K., Thomas, Patrick B., Seim, Inge, Jeffery, Penny L., Gahete, Manuel D., Maugham, Michelle, Crisp, Gabrielle J., Stacey, Andrew, Shah, Esha T., Walpole, Carina, Whiteside, Eliza J., Nelson, Colleen C., Herington, Adrian C., Luque, Raúl M., Veedu, Rakesh N., and Chopin, Lisa K.

Abstract

Recent evidence suggests that numerous long non-coding RNAs (lncRNAs) are dysregulated in cancer, and have critical roles in tumour development and progression. The present study investigated the ghrelin receptor antisense lncRNA growth hormone secretagogue receptor opposite strand (GHSROS) in breast cancer. Reverse transcription-quantitative polymerase chain reaction revealed that GHSROS expression was significantly upregulated in breast tumour tissues compared with normal breast tissue. Induced overexpression of GHSROS in the MDA-MB-231 breast cancer cell line significantly increased cell migration in vitro, without affecting cell proliferation, a finding similar to our previous study on lung cancer cell lines. Microarray analysis revealed a significant repression of a small cluster of major histocompatibility class II genes and enrichment of immune response pathways; this phenomenon may allow tumour cells to better evade the immune system. Ectopic overexpression of GHSROS in the MDA-MB-231 cell line significantly increased orthotopic xenograft growth in mice, suggesting that in vitro culture does not fully capture the function of this lncRNA. This study demonstrated that GHSROS may serve a relevant role in breast cancer. Further studies are warranted to explore the function and therapeutic potential of this lncRNA in breast cancer progression.

Published
2019

18. No effect of unacylated ghrelin administration on subcutaneous PC3 xenograft growth or metabolic parameters in a Rag1-/- mouse model of metabolic dysfunction

Author

Maugham, Michelle L., primary, Seim, Inge, additional, Thomas, Patrick B., additional, Crisp, Gabrielle J., additional, Shah, Esha T., additional, Herington, Adrian C., additional, Brown, Kristy A., additional, Gregory, Laura S., additional, Nelson, Colleen C., additional, Jeffery, Penny L., additional, and Chopin, Lisa K., additional

Published
2018
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19. Limited short-term effects on human prostate cancer xenograft growth and epidermal growth factor receptor gene expression by the ghrelin receptor antagonist [D-Lys3]-GHRP-6

Author

Maugham, Michelle L., primary, Seim, Inge, additional, Thomas, Patrick B., additional, Crisp, Gabrielle J., additional, Shah, Esha T., additional, Herington, Adrian C., additional, Gregory, Laura S., additional, Nelson, Colleen C., additional, Jeffery, Penny L., additional, and Chopin, Lisa K., additional

Published
2018
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21. No effect of administration of unacylated ghrelin on subcutaneous PC3 xenograft growth in a Rag1−/− mouse model of metabolic dysfunction

Author

Maugham, Michelle L., primary, Seim, Inge, additional, Thomas, Patrick B., additional, Crisp, Gabrielle J., additional, Shah, Esha T., additional, Herington, Adrian C., additional, Brown, Kristy A., additional, Gregory, Laura S., additional, Nelson, Colleen C., additional, Jeffery, Penny L., additional, and Chopin, Lisa K., additional

Published
2018
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24. Abstract 4819: Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

Author

Maugham, Michelle L., primary, Thomas, Patrick B., additional, Crisp, Gabrielle J., additional, Philp, Lisa K., additional, Shah, Esha T., additional, Herington, Adrian C., additional, Chen, Chen, additional, Gregory, Laura S., additional, Nelson, Colleen C., additional, Seim, Inge, additional, Jeffery, Penny L., additional, and Chopin, Lisa K., additional

Published
2017
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25. Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

Author

Maugham, Michelle L., primary, Thomas, Patrick B., additional, Crisp, Gabrielle J., additional, Philp, Lisa K., additional, Shah, Esha T., additional, Herington, Adrian C., additional, Chen, Chen, additional, Gregory, Laura S., additional, Nelson, Colleen C., additional, Seim, Inge, additional, Jeffery, Penny L., additional, and Chopin, Lisa K., additional

Published
2017
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26. Limited short-term effects on human prostate cancer xenograft growth and epidermal growth factor receptor gene expression by the ghrelin receptor antagonist [D-Lys3]-GHRP-6.

Author

Maugham, Michelle L., Seim, Inge, Thomas, Patrick B., Crisp, Gabrielle J., Shah, Esha T., Herington, Adrian C., Gregory, Laura S., Nelson, Colleen C., Jeffery, Penny L., and Chopin, Lisa K.

Abstract

Purpose: The ghrelin axis regulates many physiological functions (including appetite, metabolism, and energy balance) and plays a role in disease processes. As ghrelin stimulates prostate cancer proliferation, the ghrelin receptor antagonist [D-Lys3]-GHRP-6 is a potential treatment for castrate-resistant prostate cancer and for preventing the metabolic consequences of androgen-targeted therapies. We therefore explored the effect of [D-Lys3]-GHRP-6 on PC3 prostate cancer xenograft growth. Methods: NOD/SCID mice with PC3 prostate cancer xenografts were administered 20 nmoles/mouse [D-Lys3]-GHRP-6 daily by intraperitoneal injection for 14 days and tumour volume and weight were measured. RNA sequencing of tumours was conducted to investigate expression changes following [D-Lys3]-GHRP-6 treatment. A second experiment, extending treatment time to 18 days and including a higher dose of [D-Lys3]-GHRP-6 (200 nmoles/mouse/day), was undertaken to ensure repeatability. Results: We demonstrate here that daily intraperitoneal injection of 20 nmoles/mouse [D-Lys3]-GHRP-6 reduces PC3 prostate cancer xenograft tumour volume and weight in NOD/SCID mice at two weeks post treatment initiation. RNA-sequencing revealed reduced expression of epidermal growth factor receptor (EGFR) in these tumours. Further experiments demonstrated that the effects of [D-Lys3]-GHRP-6 are transitory and lost after 18 days of treatment. Conclusions: We show that [D-Lys3]-GHRP-6 has transitory effects on prostate xenograft tumours in mice, which rapidly develop an apparent resistance to the antagonist. Although further studies on [D-Lys3]-GHRP-6 are warranted, we suggest that daily treatment with the antagonist is not a suitable treatment for advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Published
2019
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27. MUC13 overexpression in renal cell carcinoma plays a central role in tumor progression and drug resistance

Author

Sheng, Yonghua, primary, Ng, Choa Ping, additional, Lourie, Rohan, additional, Shah, Esha T., additional, He, Yaowu, additional, Wong, Kuan Yau, additional, Seim, Inge, additional, Oancea, Iulia, additional, Morais, Christudas, additional, Jeffery, Penny L., additional, Hooper, John, additional, Gobe, Glenda C., additional, and McGuckin, Michael A., additional

Published
2017
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29. Genome-wide gain-of-function screen for genes that induce epithelial-to-mesenchymal transition in breast cancer

Author

Škalamera, Dubravka, primary, Dahmer-Heath, Mareike, additional, Stevenson, Alexander J., additional, Pinto, Cletus, additional, Shah, Esha T., additional, Daignault, Sheena M., additional, Said, Nur Akmarina B.M., additional, Davis, Melissa, additional, Haass, Nikolas K., additional, Williams, Elizabeth D., additional, Hollier, Brett G., additional, Thompson, Erik W., additional, Gabrielli, Brian, additional, and Gonda, Thomas J., additional

Published
2016
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31. No effect of unacylated ghrelin administration on subcutaneous PC3 xenograft growth or metabolic parameters in a Rag1-/- mouse model of metabolic dysfunction.

Author

Maugham, Michelle L., Seim, Inge, Thomas, Patrick B., Crisp, Gabrielle J., Shah, Esha T., Herington, Adrian C., Brown, Kristy A., Gregory, Laura S., Nelson, Colleen C., Jeffery, Penny L., and Chopin, Lisa K.

Subjects
GHRELIN, XENOGRAFTS, HIGH-fat diet, METABOLIC syndrome, PROSTATE cancer
Abstract

Ghrelin is a peptide hormone which, when acylated, regulates appetite, energy balance and a range of other biological processes. Ghrelin predominately circulates in its unacylated form (unacylated ghrelin; UAG). UAG has a number of functions independent of acylated ghrelin, including modulation of metabolic parameters and cancer progression. UAG has also been postulated to antagonise some of the metabolic effects of acyl-ghrelin, including its effects on glucose and insulin regulation. In this study, Rag1-/- mice with high-fat diet-induced obesity and hyperinsulinaemia were subcutaneously implanted with PC3 prostate cancer xenografts to investigate the effect of UAG treatment on metabolic parameters and xenograft growth. Daily intraperitoneal injection of 100 μg/kg UAG had no effect on xenograft tumour growth in mice fed normal rodent chow or 23% high-fat diet. UAG significantly improved glucose tolerance in host Rag1-/- mice on a high-fat diet, but did not significantly improve other metabolic parameters. We propose that UAG is not likely to be an effective treatment for prostate cancer, with or without associated metabolic syndrome. [ABSTRACT FROM AUTHOR]

Published
2018
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33. hSSB1 (NABP2/OBFC2B) modulates the DNA damage and androgen-induced transcriptional response in prostate cancer

Author

Mark N. Adams, Laura V. Croft, Aaron Urquhart, Mohamed Ashick Mohamed Saleem, Anja Rockstroh, Pascal H. G. Duijf, Patrick B. Thomas, Genevieve P. Ferguson, Idris Mohd Najib, Esha T. Shah, Emma Bolderson, Shivashankar Nagaraj, Elizabeth D. Williams, Colleen C. Nelson, Kenneth J. O'Byrne, Derek J. Richard, Adams, Mark N, Croft, Laura V, Urquhart, Aaron, Saleem, Mohamed Ashick Mohamed, Rockstroh, Anja, Duijf, Pascal HG, Thomas, Patrick B, Ferguson, Genevieve P, Najib, Idris Mohd, Shah, Esha T, Bolderson, Emma, Nagaraj, Shivashankar, Williams, Elizabeth D, Nelson, Colleen C, O'Byrne, Kenneth J, and Richard, Derek J

Subjects
radiation, Oncology, Urology, androgen receptor, DNA damage, hSSB1/NABP2, prostate cancer
Abstract

Background: Activation and regulation of androgen receptor (AR) signaling and the DNA damage response impact the prostate cancer (PCa) treatment modalities of androgen deprivation therapy (ADT) and radiotherapy. Here, we have evaluated a role for human single-strand binding protein 1 (hSSB1/NABP2) in modulation of the cellular response to androgens and ionizing radiation (IR). hSSB1 has defined roles in transcription and maintenance of genome stability, yet little is known about this protein in PCa. Methods: We correlated hSSB1 with measures of genomic instability across available PCa cases from The Cancer Genome Atlas (TCGA). Microarray and subsequent pathway and transcription factor enrichment analysis were performed on LNCaP and DU145 prostate cancer cells. Results: Our data demonstrate that hSSB1 expression in PCa correlates with measures of genomic instability including multigene signatures and genomic scars that are reflective of defects in the repair of DNA double-strand breaks via homologous recombination. In response to IR-induced DNA damage, we demonstrate that hSSB1 regulates cellular pathways that control cell cycle progression and the associated checkpoints. In keeping with a role for hSSB1 in transcription, our analysis revealed that hSSB1 negatively modulates p53 and RNA polymerase II transcription in PCa. Of relevance to PCa pathology, our findings highlight a transcriptional role for hSSB1 in regulating the androgen response. We identified that AR function is predicted to be impacted by hSSB1 depletion, whereby this protein is required to modulate AR gene activity in PCa. Conclusions: Our findings point to a key role for hSSB1 in mediating the cellular response to androgen and DNA damage via modulation of transcription. Exploiting hSSB1 in PCa might yield benefits as a strategy to ensure a durable response to ADT and/or radiotherapy and improved patient outcomes. Refereed/Peer-reviewed

Published
2023

34. Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

Author

Kenneth J. O'Byrne, Pascal H.G. Duijf, Mark N. Adams, Sam Beard, Christopher Molloy, Eric D. Boittier, Derek J. Richard, Joshua T. Burgess, Emma Bolderson, Katherine B. Sahin, Neha S. Gandhi, Katrina Kildey, Esha T. Shah, Amila Suraweera, Kildey, Katrina, Gandhi, Neha S, Sahin, Katherine B, Shah, Esha T, Boittier, Eric, Duijf, Pascal HG, Molloy, Christopher, Burgess, Joshua T, Beard, Sam, Bolderson, Emma, Suraweera, Amila, Richard, Derek J, O'Byrne, Kenneth J, and Adams, Mark N

Subjects
0301 basic medicine, Lung Neoplasms, medicine.medical_treatment, Medicine (miscellaneous), Cell Cycle Proteins, Biomarkers, Pharmacological, chemistry.chemical_compound, Prognostic markers, 0302 clinical medicine, Maintenance therapy, Carcinoma, Non-Small-Cell Lung, Databases, Genetic, CDCA3 protein, Medicine, platinum, Biology (General), Casein Kinase II, biology, Cell Cycle, Cadherins, Ubiquitin ligase, 030220 oncology & carcinogenesis, Casein kinase 2, General Agricultural and Biological Sciences, medicine.drug, QH301-705.5, General Biochemistry, Genetics and Molecular Biology, Article, Genomic Instability, 03 medical and health sciences, Drug Therapy, Antigens, CD, Cell Line, Tumor, Humans, Lung cancer, Cell Proliferation, Platinum, Cisplatin, Chemotherapy, non small cell lung cancer, business.industry, Immunotherapy, medicine.disease, Carboplatin, 030104 developmental biology, chemistry, Drug Resistance, Neoplasm, biology.protein, Cancer research, business, Non-small-cell lung cancer
Abstract

Platinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients., Kildey et al find that high levels of mitotic regulator CDCA3 correlates with sensitivity to platinum agents in non-small cell lung cancer patients and cell lines. They show that interfering with CDCA3 degradation through CK2 inhibition enhances CDCA3 levels and increases sensitivity to platinum agents suggesting a therapeutic route.

Published
2021

35. Genome-wide gain-of-function screen for genes that induce epithelial-to-mesenchymal transition in breast cancer

Author

Esha T. Shah, Brett G. Hollier, Melissa J. Davis, Nikolas K. Haass, Mareike Dahmer-Heath, Erik W. Thompson, Dubravka Škalamera, Cletus Pinto, Brian Gabrielli, Alexander J. Stevenson, Nur Akmarina B.M. Said, Elizabeth D. Williams, S. M. Daignault, Thomas J. Gonda, Škalamera, Dubravka, Dahmer-Heath, Mareike, Stevenson, Alexander J, Pinto, Cletus, Shah, Esha T, Daignault, Sheena M, Said, Nur Akmarina BM, Davis, Melissa, Haass, Nikolas K, Williams, Elizabeth D, Hollier, Brett G, Thompson, Erik W, Gabrielli, Brian, and Gonda, Thomas J

Subjects
0301 basic medicine, Epithelial-Mesenchymal Transition, epithelial-mesenchymal transition, Vimentin, lentiviral vectors, Breast Neoplasms, Metastasis, 03 medical and health sciences, Open Reading Frames, vimentin, breast cancer, Antigens, CD, Cell Line, Tumor, Medicine, Humans, Epithelial–mesenchymal transition, high-content-screening, Gene, biology, business.industry, Cadherin, Genome, Human, Gene Expression Profiling, Mesenchymal stem cell, Lentivirus, Cancer, Epithelial Cells, medicine.disease, Cadherins, Gene expression profiling, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, Cancer research, biology.protein, Disease Progression, Female, business, Research Paper, Genome-Wide Association Study, Plasmids
Abstract

Epithelial to mesenchymal transition (EMT) is a developmental program that has been implicated in progression, metastasis and therapeutic resistance of some carcinomas. To identify genes whose overexpression drives EMT, we screened a lentiviral expression library of 17000 human open reading frames (ORFs) using high-content imaging to quantitate cytoplasmic vimentin. Hits capable of increasing vimentin in the mammary carcinoma-derived cell line MDA-MB-468 were confirmed in the non-tumorigenic breast-epithelial cell line MCF10A. When overexpressed in this model, they increased the rate of cell invasion through Matrigel™, induced mesenchymal marker expression and reduced expression of the epithelial marker E-cadherin. In gene-expression datasets derived from breast cancer patients, the expression of several novel genes correlated with expression of known EMT marker genes, indicating their in vivo relevance. As EMT-associated properties are thought to contribute in several ways to cancer progression, genes identified in this study may represent novel targets for anti-cancer therapy. Refereed/Peer-reviewed

Published
2016

36. The long non-coding RNA GHSROS facilitates breast cancer cell migration and orthotopic xenograft tumour growth.

Author

Thomas PB, Seim I, Jeffery PL, Gahete MD, Maugham M, Crisp GJ, Stacey A, Shah ET, Walpole C, Whiteside EJ, Nelson CC, Herington AC, Luque RM, Veedu RN, and Chopin LK

Subjects
Animals, Apoptosis genetics, Breast pathology, Breast Neoplasms immunology, Breast Neoplasms pathology, Disease Progression, Down-Regulation, Female, Gene Expression Profiling, Histocompatibility Antigens Class II genetics, Histocompatibility Antigens Class II immunology, Humans, MCF-7 Cells, Mice, Middle Aged, Oligonucleotide Array Sequence Analysis, Receptors, Ghrelin genetics, Tumor Escape genetics, Xenograft Model Antitumor Assays, Breast Neoplasms genetics, Cell Movement genetics, Gene Expression Regulation, Neoplastic, RNA, Long Noncoding metabolism
Abstract

Recent evidence suggests that numerous long non‑coding RNAs (lncRNAs) are dysregulated in cancer, and have critical roles in tumour development and progression. The present study investigated the ghrelin receptor antisense lncRNA growth hormone secretagogue receptor opposite strand (GHSROS) in breast cancer. Reverse transcription‑quantitative polymerase chain reaction revealed that GHSROS expression was significantly upregulated in breast tumour tissues compared with normal breast tissue. Induced overexpression of GHSROS in the MDA‑MB‑231 breast cancer cell line significantly increased cell migration in vitro, without affecting cell proliferation, a finding similar to our previous study on lung cancer cell lines. Microarray analysis revealed a significant repression of a small cluster of major histocompatibility class II genes and enrichment of immune response pathways; this phenomenon may allow tumour cells to better evade the immune system. Ectopic overexpression of GHSROS in the MDA‑MB‑231 cell line significantly increased orthotopic xenograft growth in mice, suggesting that in vitro culture does not fully capture the function of this lncRNA. This study demonstrated that GHSROS may serve a relevant role in breast cancer. Further studies are warranted to explore the function and therapeutic potential of this lncRNA in breast cancer progression.

Published
2019
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