Dr Lilian Soon
Position
Lecturer, Structural Biology
Contact
Email:
Ph: + 61 2 9351 5322
Fax: + 61 2 9351 7682
Qualifications
Ordinary Degree of Bachelor of Science, 1991; Honours Degree of Bachelor of Science, 1993; Degree of Doctor of Philosophy, 1997.
Background
Fogarty International Fellow at the Laboratory of Cellular and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD, USA, 1997; Research Associate at the Department of Pulmonary and Critical Care, Faculty of Medicine, New York Univerisity, NY, USA, 2001-2003; Research Associate at the Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY, USA, 2003-2005.
Research interests
Our long-term goal is to elucidate the regulation of cancer cell motility and to derive therapeutic strategies from this knowledge. Modes of cancer cell motility include (i) chemokinesis characterized by a change in cell speed or direction in the absence of a gradient of chemoattractant, (ii) chemotaxis known as motility towards a gradient and (iii) rapid, linear walking along collagen fibers observed in vivo. We hypothesize that mechanisms of chemokinesis and chemotaxis are linked to in vivo linear walking and together form crucial aspects of metastasis. The a priori reasons are:
- first, our research shows that the most invasive carcinoma cells are highly chemokinetic (Tchou-Wong 2005, submitted paper);
- second, chemotaxis is required for homing during metastasis;
- third, intravital tumor imaging reveals that cancer cells move along collagen fibres at speeds ten times faster than observed in vitro.
- Furthermore, collagen fibres often intersect with blood vessels providing routes to sites of intravasation.
Elucidation of mechanisms of chemokinesis and metastasis.
We explored the heterogeneity of a lung cancer cell line and succeeded in isolating a supopulation of highly chemokinetic and invasive cells. Microarray analyses showed differential gene profiles between the chemokinetic subpopulation and the original cell line. Real-time PCR confirmed that a gene, reduced in-random motile (ROM), was downregulated in chemokinetic cells as well as in a panel of lung cancer cells compared to control or normal cells. Disruption of ROM function by mutagenesis resulted in increased invasion and chemokinesis with no effect on chemotaxis. Ongoing studies serve to characterize the function of ROM in the regulation of speed, polarity, motility and metastasis in cancer cells.
Elucidation of mechanisms of chemotaxis and metastasis.
We are developing a novel chemotaxis chamber to record and observe the chemotaxis of cancer cells under high-resolution microscopy (Soon et al., 2005, paper submitted). The proteins along the EGFR/Cdc42/N-WASP/Arp2/3 axis will be evaluated for function in navigation or directionality of cancer cell chemotaxis along an EGF gradient.
Intravital Imaging of tumour cell motility along collagen fibres.
Multiphoton imaging of live tumors is a powerful method of studying the motility and invasion of carcinoma cells in vivo. Knockdown of ROM and N-WASP in fluorescent, GFP-expressing cancer cells will be accomplished by stable siRNA transfections. The function of these genes on the speed and directionality of motility along collagen fibres will be studied.
Selected publications
| View Lilian’s publications listing on PubMed |
- Tchou-Wong, K.M., Pixley, F., Condeelis, J., Rubin, J.,Rom, W., Soon, L.L. (2005). Heterogeneity in lung cancer cells: characterization of a hypermotile subpopulation and correlation with the invasive potential of cancer cells. Oncogene. Paper submitted.
- Soon, L.L, Mouneimne, G., Segall, J., Wyckoff, J., Condeelis, J. (2005). "Characterization of the Soon assay for viewing of cancer cell chemotaxis." Cell Motil Cytoskeleton. Paper submitted.
- Mouneimme, G., Soon, L.L., DesMarais, V., Sidani, M., Song, X., Yip, S., Ghosh, M., Eddy, R., Backer, J.M., Condeelis, J. (2004). Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation. J Cell Biol 166:1-12.
- Soon, L. L., Yie, T.A., Shvarts, A., Levine, A.J., Su, F., Tchou-Wong, K.M. (2003). Overexpression of WISP-1 down-regulated motility and invasion of lung cancer cells through inhibition of Rac activation. J Biol Chem 278:11465-11470.