Gene Regulation in Cancer Laboratory
Research Program Overview:
Breast and prostate cancers are among the most frequently diagnosed cancers. At early stages, these cancers are often treatable, but when they progress to metastatic disease treatment options are limited and less effective. Our research aims to better understand how cancer cells gain aggressive properties to aid in the development of more effective treatments.
As cancers become more aggressive, tumour cells undergo significant changes in their function. For epithelial tumour cells to metastasise they acquire abilities to invade, survive and then colonise distant sites. Cancer cell plasticity (often referred to as epithelial-mesenchymal transition or EMT) plays a major role in the metastatic cascade. Our lab examines how EMT and cancer metastasis are regulated by changes in the coding and non-coding transcriptome. In particular, our research aims to understand how microRNAs and RNA binding proteins influence the cancer cell transcriptome and cell function. To achieve this, we utilise a range of in vitro and in vivo cancer models, gene manipulation techniques (including CRISPR), and advanced sequencing methods.
Current Research Projects:
- Understanding how RNA binding proteins and alternative splicing contribute to cancer cell plasticity underlying prostate cancer progression and resistance to therapies
- Regulation of epithelial-mesenchymal transition by novel proteins
- The function of microRNAs in breast cancer metastasis
Select Recent Publications:
- Neumann DP, Goodall GJ, Gregory PA (2022) The Quaking RNA-binding proteins as regulators of cell differentiation. WIREs RNA
- Chi LH, Cross RSN, Redvers RP, Davis M, Hediyeh-Zadeh S, Mathivanan S, Samuel M, Lucas EC, Mouchemore K, Gregory PA, Johnstone CN, Anderson RL (2022) MicroRNA-21 is immunosuppressive and pro-metastatic via separate mechanisms. Oncogenesis 11(1):38.
- Chan KM, Gleadle JM, Gregory PA, Phillips CA, Shirazi HS, Whiteley A, Li, J, Vasilev K, MacGregor M (2021) Selective Microfluidic Capture and Detection of Prostate Cancer Cells from Urine without Digital Rectal Examination. 13(21):5544.
- Gregory PA (2019) The miR-200-Quaking axis functions in tumour angiogenesis. Oncogene. 38(41):6767-6769.
- Pillman KA, Phillips CA, Roslan S, Toubia J, Dredge BK, Bert AG, Lumb R, Neumann DP, Li X, Conn SJ, Liu D, Bracken CP, Lawrence DM, Stylianou N, Schreiber AW, Tilley WD, Hollier BG, Khew-Goodall Y, Selth LA, Goodall GJ, Gregory PA (2018) miR-200/375 controls epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking. EMBO J. Jul 2;37(13). pii: e99016.
- Selth LA, Das R, Townley SL, Coutinho I, Hanson AR, Centenera MM, Stylianou N, Sweeney K, Soekmadji C, Jovanovic L, Nelson CC, Zoubeidi A, Butler LM, Goodall GJ, Hollier BG, Gregory PA, Tilley WD (2017) A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer. Oncogene 36(1):24-34.
- Conn SC, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA, Goodall GJ (2015) The RNA binding protein Quaking regulates formation of circRNAs. Cell 160(6):1125-34.
- Li X, Roslan S, Johnstone CN, Wright JA, Bracken CP, Anderson M, Bert AG, Selth LA, Robin Anderson RL, Goodall GJ, Gregory PA*, Khew-Goodall Y* (2014) MiR-200 can repress breast cancer metastasis through ZEB1-independent, but moesin-dependent pathways. Oncogene 33(31):4077-88.
- Kolesnikoff N, Attema JL, Roslan S, Bert AG, Schwarz QP, Gregory PA*, Goodall GJ* (2014) Specificity protein 1 (Sp1) maintains basal epithelial expression of the miR-200 family: implications for epithelial-mesenchymal transition. Biol. Chem. 289(16):11194-205.
- Gregory PA, Bracken CP, Smith E, Bert AG, Wright JA, Roslan S, Morris M, Wyatt L, Farshid G, Lim Y-Y, Lindeman GJ, Shannon MF, Drew PA, Khew-Goodall Y, Goodall GJ (2011) An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Biol. Cell. 22(10):1686-98. *Featured front cover article.
- Bracken CP*, Gregory PA*, Kolesnikoff N*, Bert AG, Shannon MF, Goodall GJ (2008) A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 68 (19): 7846-7854.
- Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell. Biol. 10, 593-601. *14th most cited Cancer paper from 2008 Nature Medicine (2011) 17(3):280