Kathryn M Taylor
PhD
Senior Research Associate

Tel:   +44 (0)29 2087 5292
email:TaylorKM@Cardiff.ac.uk

For other TCCR staff, see stafflist

Research interests

Tenovus is commited to a programme of novel gene identification in prostate and breast cancer. This programme uses 'state of the art' technologies such as arrays as major tools for identifying interesting or novel genes that are altered in disease states. Once these genes or proteins have been identified, they are investigated at the protein level to provide information of function and ultimately confirm a link with disease. The use of recombinant expression systems can be a useful tool for gathering such information. Recently, I have been closely involved with the development of suitable expression technologies for a number of potentially interesting genes.

Present Research

The role of oestrogen-regulated LIV-1 in metastatic breast cancer.
My main interest is in the investigation of LIV-1 function, an oestrogen-regulated gene which has been implicated in metastatic breast cancer. We are investigating the new LIV-1 subfamily to characterise both the cellular and molecular biology. This will help in our quest to ultimately define the role of LIV-1 in metastatic breast cancer and produce a suitable prognostic marker for disease.

The LIV-1 subfamily of zinc transporters.

LIV-1 is an oestrogen-regulated gene that has been implicated in metastatic breast cancer. Its detection was associated with oestrogen receptor positive breast cancer and with the metastatic spread of these cancers to the regional lymph nodes. Subsequent computer searches of secondary structure predicted LIV-1 to contain 8 transmembrane domains, a long extracellular N-terminus, a short extracellular C-terminus, a consensus sequence for ZIP zinc transporters and a consensus sequence for the catalytic zinc-binding site of metalloproteases, (HEXXH, where H = histidine, E = glutamic acid and X = any amino acid). This latter motif was unusual in that it also contained two novel residues (HEXPHE), proline (P) and glutamic acid (E), previously unprecedented in these positions in any other metalloprotease motifs [alignment]. Searching the non-redundant NCBI database using BLAST and the unique HEXPHEXGD motif of LIV-1, we have identified 39 sequences from 12 species, including human, mouse, C.elegans, Drosophila, yeast and bacteria, that contain this unique and highly conserved motif [ZIP tree]. We call this new subfamily LZT, for LIV-1 subfamily of ZIP zinc Transporters [LZT tree].

LZT proteins are similar to ZIP transporters in secondary structure [schematic] and ability to transport metal ions into the cytosol across the plasma membrane or intracellular membranes. The localisation of LZT proteins to lamellipodiae mirrors cellular location of the membrane-type matrix metalloproteases [lamelli]. These differences to other zinc transporters may be consistent with an alternative role for LZT proteins in cells, particularly in diseases such as cancer.
There are 9 human LZT family members [LZT tree] and we are currently investigating whether they also have a role in breast cancer.

Technologies used

Engineering transmembrane deletion mutants using TOPO-TA cloning and PCR.
Mammalian (CHO) and insect (Schneider S2) cell transfection with recombinant tags to enable detection.
SDS-PAGE, Western Blotting, FACS, immunocytochemistry.
Confocal imaging of cells using fluorescent agents .
Real-time monitoring of Zn2+ concentrations in cells using Newport Green and Zinquin.
Site-directed mutagenesis and cloning of recombinant proteins.
Expression of recombinant proteins using Baculovirus infection of insect cells (Trichoplusia ni) and adenovirus infection of mammalian (HeLa) cells.

Other Responsibilities

Tenovus Health and Safety Officer
Tenovus Biological Safety Officer
Pharmacy Biological Safety Supervisor

Funding

At present this work is funded by the Tenovus Cancer Charity.

Recent Publications

Thomas NB Hutcheson IR, Campbell L, Gee J, Taylor K M, Nicholson RI, Gumbleton M (2009) Suppression of Caveolin-1 is associated with Tamoxifen Resistance in MCF-7 breast cancer cells, Breast Cancer Research and Treatment, in press

Nicholson RI, Hutcheson IR, Hiscox S, Taylor KM, Gee JMW (2009) Experimental endocrine resistance: concepts and strategies, in therapeutic resistance to anti-hormonal drugs in breast cancer, new molecular aspects and their potential as targets, Ed. Hiscox S, Gee J, Nicholson RI, Springer, DOI 10.1007/978-1-4020-8526-0.

Hogstrand C, Kille P, Nicholson RI, Taylor KM, (2009) Zinc transporters and Cancer: A potential role for ZIP7 as a hub for tyrosine kinase activation, Trends Mol Med, 15,101-111

Taylor KM, (2008) A distinct role in breast cancer for two LIV-1 family zinc transporters, Biochem Soc Trans, 36 (Pt6), 1247-51.

Taylor, K.M, Vichova, P., Jordan, N., Hiscox, S., Hendley, R. and Nicholson, R. (2008) ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in anti-hormone resistant breast cancer cells. Endocrinology. 149(10):4912-20.

Hiscox, S., Jordan, N.J., Smith, C., James, M., Morgan, L., Taylor, K.M., Green, T.P., Nicholson, R.I. (2008) Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells. Breast Cancer Res Treat. In press. doi:10.1007/s10549-008-0058-6.

Taylor, K.M., Morgan, H.E., Smart K, Zahari NM, Pumford S, Ellis IO, Robertson JFR, Nicholson RI, (2007) The emerging role of the LIV-1subfamily of zinc transporters in breast cancer, Molecular Medicine, 13 l (7-8): 396-406.

Zhao L, Chen W, Taylor KM, Cai B, Li X. (2007) LIV-1 suppression inhibits HeLa cell invasion by targeting ERK1/2-Snail/Slug pathway. Biochem Biophys Res Commun. 363(1):82-88.

RI Nicholson, IR Hutcheson, HE Jones, SE Hiscox, M Giles, K M Taylor and JMW Gee (2007) Growth factor signalling in endocrine and anti-growth factor resistant breast cancer, Rev Endocr Metab Disord. 8(3):241-53. Review.

Taylor, K. & Nicholson, R. (2006). Fear of intimacy - a close LIV-1 acquaintancy? Development, 133, 3053.

Hiscox S., Jiang W.G., Obermeier K., Taylor K., Morgan L., Burmi R., Barrow D. & Nicholson R.I. (2006). Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation. Int J Cancer, 118,
290-301.

Jones H.E., Gee J.M., Taylor K.M., Barrow D., Williams H.D., Rubini M. & Nicholson R.I. (2005). Development of strategies for the use of anti-growth factor treatments. Endocr Relat Cancer, 12 Suppl 1, S173-82.

Taylor K.M., Morgan H.E., Johnson A. & Nicholson R.I. (2004) Structure-function analysis of a novel member of the LIV-1 subfamily of zinc transporters, ZIP14. Febs Letters

Taylor K.M., Hiscox S. & Nicholson R.I. (2004). Zinc transporter LIV-1: A link between cellular development and cancer progression. Trends in Endocrinology and Metabolism, 15 (10); 461-463

Taylor K.M., Morgan H.E., Johnson A. & Nicholson R.I. (2004). Structure-Function Analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters. Biochem J. 377(1), 131-139.

Taylor, K. M., Morgan, H. E., Johnson, A., Hadley, L. J., & Nicholson, R.I., (2003). Structure-Function Analysis of LIV-1, the breast cancer associated protein that belongs to a new subfamily of zinc transporters. Biochem. J. 375 (1), 51-59.

Taylor K.M. ,Nicholson R.I. (2003). The LZT proteins; the new LIV-1 subfamily of zinc transporters. BBA 1611 16-30 (2003)

Glynne-Jones E., Harper M.E., Seery L.T., James R., Anglin I., Morgan H.E., Taylor K.M., Gee J.M., Nicholson RI (2001). TENB2, a proteoglycan identified in prostate cancer that is associated with disease progression and androgen independence . Int. J. Cancer 94, 178-184.

Taylor K.M. (2000). LIV-1 breast cancer protein belongs to a new family of histidine-rich membrane proteins with potential to control intracellular Zn++ homeostasis. IUBMBLife, 49(4), 249-253.

Presentations at conferences

Taylor, KM., Invited oral presentation at Rank Prize Fund Mini-symposium on Micronutrients in Animals and Plants in Grasmere, October 2008 entitled The LIV-1 family of zinc transporters and their role in cancer’.

Taylor, KM., Invited oral presentation at Biochemical Society meeting Metal metabolism: transport, development and neurodegeneration at Imperial College, May, 2008, entitled ‘The emerging role of zinc transporters in breast cancer’.

Taylor, KM, Jordan, N., Hiscox, S., and Nicholson, RI at Biochemical Society meeting Metal metabolism: transport, development and neurodegeneration at Imperial College, May, 2008 entitled ‘ZIP7 controls intracellular zinc distribution providing a breast cancer target’.

Taylor, KM, Jordan, N., Hiscox, S., Gee, JMW., and Nicholson, RI at the Breast Cancer Campaign annual conference at the Royal Society, London, May 2008 entitled ‘The zinc transporter HKE4 as a new target in anti-hormone resistant breast cancer’.

Taylor, KM., Invited oral presentation at International Society for Zinc Biology, Banff, February, 2008, entitled ‘a central role for HKE4/ZIP7 in zinc-dependant signalling in breast cancer’.

Taylor KM, Vichova P, Hiscox S and Nicholson RI Zinc-dependant stimulation of Src, EGFR and IGFR signalling pathways in Tamoxifen-resistant breast cancer and the role of zinc transporters. 2nd AstraZeneca/Tenovus cancer conference, Cardiff, 2006.

Taylor KM, Zahari NM, Vichova P. and Nicholson RI Involvement Of Zinc Transporter HKE4 In Tamoxifen-Resistant Breast Cancer. 2nd AstraZeneca/Tenovus cancer conference, Cardiff, 2006.

Taylor KM, invited oral presentation ‘The LIV-1 subfamily as new targets in anti-hormone resistance and metastasis of breast cancer’, at Zinc Signals, Siena, Italy, 2006.

Vichova P, Taylor KM, and Nicholson RI. (2005) Zinc-dependant activation of c-Src, EGFR and IGF-1R mitogenic pathways in tamoxifen-resistant breast cancer cells. 9th Nottingham International Breast Cancer Conference, Nottingham, UK.

Taylor KM, Vichova P, Hiscox S, and Nicholson RI. (2005) Zinc-dependant activation of EGFR and co-localisation with vinculin in focal adhesions in Tamoxifen resistant breast cancer cells. Beatson Cancer Conference, Glasgow.

Scheper M, Nikitakis NG, Siavash H, Gupta A, Taylor KM, Sauk JJ. (2005) LIV-1, a potential novel immunohistochemical marker for salivary gland tumors, IADR conference.

Taylor KM, Vichova P and Nicholson RI (2005) Activation of EGFR in Tamoxifen resistant breast cancer by a zinc-dependant Src kinase mechanism. 1st AstraZeneca/Tenovus cancer conference, Cardiff.

Taylor, K M. Invited oral presentation ‘Characterisation of the new LIV-1 subfamily of ZIP transporters and their role in breast cancer’. at Zinc Signals Aarhus, Denmark, 2004.

Taylor KM invited oral presentation ‘The LIV-1 Subfamily of Zinc Transporters’ at IRG on ionic signalling and health, Cardiff University, 2003.

Taylor KM invited oral presentation ‘The LIV-1 Subfamily of Zinc Transporters’ at Cardiff Biomedical Imaging Forum, Cardiff University, 2003.

Abstracts

Taylor K.M., & Nicholson R.I. (2002)
The LIV-1 subfamily of ZIP transporters have a unique metalloprotease motif, HEXPHEXGD. Biochemical Society, December, 2002

Taylor K.M., Morgan H.E., & Nicholson R.I. (2001)
LIV-1 breast cancer protein belongs to a new family of membrane proteins with potential for metalloprotease activity and/or zinc transport. Poster at 2001 SEB Annual Meeting, Canterbury, UK, 2 -6 April 2001.

Taylor K.M., Morgan H., Hallett M.B.& Nicholson R.I., (2000)
LIV-1 breast cancer protein belongs to a new family of histidine-rich transmembrane proteins with potential to control intracellular Zn++ . Poster at VIII international congress of the Metastasis Research Society, Imperial College, London 24-27 Sept 2000.

Taylor K.M., Morgan H., & Nicholson R.I., (2000)
LIV-1 breast cancer protein belongs to a new family of histidine-rich membrane proteins with potential to control intracellular Zn++ . Poster at 18th International congress of Biochemistry and Molecular Biology, Birmingham, UK, 16-20 July, 2000.

Morgan H.E., Johnson A., Joyce E., Nicholson R.I. & Taylor K.M. (2000)
The breast cancer protein LIV-1: Investigation of function using homologous family members. Poster at 18th International congress of Biochemistry and Molecular Biology, Birmingham, UK, 16-20 July, 2000.

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