SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R C E L L B I O L O G Y P R O G R A M
HIGHLIGHTS/DISCOVERIES
• Observed the attachment of centrosomes to IF.
Although the implications of the mechanism of
detachment during mitosis are still to be assessed,
this may be relevant for cancer therapy.
OLUWATOYIN SHONUKAN, M.D.
Assistant Professor of Medicine
DESCRIPTION OF RESEARCH
Malignant melanoma arises from the melanocytes,
cells that originate in the neural
crest. Normal melanocyte development in the
neural crest and subsequent migration of the
melanocyte precursors into the skin require
trophic signals from the neurotrophin family
of growth factors. With terminal differentiation,
melanocytes lose expression of neurotrophin
receptors. Following transformation, however,
melanoma cells aberrantly express the receptors
for the neurotrophins, with more advanced stages
of the disease being more likely to express the
neurotrophin receptors than the earlier stages.
Dr. Shonukan’s research discovered that the
melanoma cells also express several members of
the neurotrophin growth factor family, thus
suggesting that the neurotrophin/neurotrophin
receptor system may be involved in the mediation
of melanoma progression. The focus of her
laboratory’s research is to understand the role
of the neurotrophins and their receptors in the
mediation of tumor progression in malignant
melanoma.
SELECTED PUBLICATIONS
2003
Shonukan, O, Bagayogo, I, McCrea, P, Chao, M,
and Hempstead, B. Neurotrophin-induced melanoma
cell migration is mediated through the actin-bundling
protein fascin. Oncogene
22:3616-23, 2003.
HIGHLIGHTS/DISCOVERIES
• Nerve growth factor (NGF), the prototypic
member of this family of growth factors, mediates
the invasiveness of melanoma cells in vitro
by inducing the coupling of the intracellular
domain of the p75 neurotrophin receptor with
the actin cytoskeleton.
• Neurotrophin-induced melanoma invasiveness
is mediated by signals generated through PI-3
kinase.
• NGF induces the disruption of cadherin-mediated
cell-cell adhesion, thereby permitting melanoma
cells to dissociate from the keratinocytes
in the epidermis and invade the dermis, from
whence they metastasize to distant sites. Dr.
Shonukan’s ongoing research efforts include
identifying the components of this pathway in
order to identify therapeutic targets.
RAKESH SINGAL, M.D.
Associate Professor of Medicine
DESCRIPTION OF RESEARCH
Dr. Singal’s research focuses on the mechanisms
that inactivate certain tumor-suppressor
genes in prostate cancer. A common mode of
such inactivation involves a modification (methylation)
in DNA. By understanding how genes are
silenced, treatments can be developed to activate
them and thereby prevent the development and/
or progression of prostate cancer. Researchers in
Dr. Singal’s laboratory also are studying methylation
of selected genes as a diagnostic and prognostic
marker in prostate cancer.
The present screening techniques for prostate
cancer are very inefficient, and two out of three
patients undergo prostate biopsy unnecessarily
to detect cancer. Cancer patients often have a
small amount of DNA circulating in their serum,
thought to be released from the cancer cells. Dr.
Singal’s laboratory has shown that certain methylated
genes are present at a substantially higher
percentage in prostate cancer tissue but not in
benign prostatic conditions. Researchers are
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 93