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
zation of microtubule dynamics. These findings
are important because little is known about the
mechanism of microtubule-dependent cell morphogenesis.
SELECTED PUBLICATIONS
2003
Wiley, DJ, Marcus, S, D’Urso, G, and Verde, F.
Control of cell polarity in fission yeast by association
of Orb6p kinase with the highly conserved
protein methyltransferase Skb1p. Journal of Biological
Chemistry 278:25256-63, 2003.
Hou, MC, Wiley, DJ, Verde, F, and McCollum,
D. Mob2p interacts with the protein kinase
Orb6p to promote coordination of cell polarity
with cell cycle progression. Journal of Cellular
Science 116:125-35, 2003.
Kim, H, Yang, P, Catanuto, P, Verde, F, Lai, H,
Du, H, Chang, F, and Marcus, S. The kelch repeat
protein, Tea1, is a potential substrate target
of the p21-activated kinase, Shk1, in the fission
yeast, Schizosaccharomyces pombe. Journal of Biological
Chemistry 278:30074-82, 2003.
HIGHLIGHTS/DISCOVERIES
• Demonstrated that Bot1 may function as a molecular
bridge between Tea1, a microtubuleassociated
protein required to establish cell
polarity and Orb6, a conserved protein kinase
related to mammalian Rho kinase and myotonic
dystrophy kinase. These findings suggest
that one of the effectors of Orb6 kinase is the
formin For3p that functions in the control of
actin cable polymerization. They also offer insight
into the hierarchy of events that lead to
polarized cell growth and in the mechanisms of
microtubule-dependent cell polarity control.
DONALD T. WEED, M.D., F.A.C.S.
Assistant Professor of Otolaryngology
DESCRIPTION OF RESEARCH
MUC4 (Sialomucin Complex) Expression in
Head and Neck Cancer
Sialomucin complex (SMC) is a novel membrane/soluble
glycoprotein complex originally
identified and isolated from membranes of
ascites sublines of the highly metastatic 13762 rat
mammary adenocarcinoma. Peptide sequence
homology between the gene product of the human
mucin MUC4 and rat SMC has recently
been reported. SMC is composed of a mucin subunit
ASGP-1 (ascites sialoglycoprotein-1) linked
to the plasma membrane via an N-glycosylated
transmembrane subunit ASGP-2. The transmembrane
subunit has two epidermal growth factor
(EGF)-like domains and can act selectively as a
ligand for the receptor tyrosine kinase ErbB2.
The mucin subunit ASGP-1 also has anti-adhesive
activity. The human MUC4 has corresponding
transmembrane (MUC4-β) and mucin
(MUC4-α) subunits, with similar growth factor
domains and anti-adhesive potential. These characteristics
suggest SMC/MUC4 plays a functional
role in normal cells by providing a direct protective
barrier at the cell surface to limit absorption
of microbes and other noxious agents to the epithelial
surface, while also participating in repair
and cell replacement processes in the epithelia as
a ligand and modulator of signaling via ErbB2.
SMC/MUC4 can participate in cell signaling
pathways via its complex with ErbB2 to mediate
pathways characterized by cell proliferation, or
pathways characterized by cell cycle inhibition
and growth arrest. Disregulation of proliferative
pathways may lead to transformation of the normal
epithelia to a neoplastic phenotype by means
of autocrine stimulation of cell growth and proliferation
via activation of ErbB2. The antiadhesive
properties of the ASGP-1/MUC4-α component
of the molecules result in reversible disruption of
integrin-mediated cell adhesion to the extracellular
matrix, and may be important in the develop-
96
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004