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alliedacademies CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11th International Conference on
J u n e 1 1 - 1 3 , 2 0 1 8 | D u b l i n , I r e l a n d
Journal of Medical Oncology and Therapeutics | Volume 3
Page 35
Although symmetrical and asymmetrical divisions of stem cells
are extensively studied in invertebrate and mammalian neural
epithelia, their role remains largely unknown in mammalian non-neural
epithelial development, regeneration and tumorigenesis. Using basal
and luminal cell-specific markers and cell lineage tracing transgenic
mice, we report that in developing prostatic epithelia, basal and luminal
cells exhibit distinct division modes. While basal cells display both
symmetric and asymmetric divisions leading to different cell fates,
luminal cells only exhibit symmetrical divisions, producing two luminal
cells. Examination of cell division modes in prostate-specific Pten mull
mice indicates that while transformed luminal cells can independently
produce tumors composed of exclusive luminal cells via symmetrical
divisions, transformed basal cells appear to generate cancer through
the daughter luminal cells derived from asymmetrical divisions. Cell
polarity and correct mitotic spindle positioning are essential for the
proper prostate epithelial cell division mode, and disruption of the two
biological features occurs at early stages in prostate tumorigenesis.
However, whether and how these two epithelial attributes are
coordinated in vivo is largely unknown. We report that conditional
genetic deletion of E-cadherin, a key component of adherens junctions,
in a mouse model results in loss of prostate luminal cell polarity
and randomization of spindle orientations. Critically, E-cadherin
ablation causes prostatic hyperplasia which progresses to invasive
adenocarcinoma. Mechanistically, E-cadherin forms a complex with
the cell polarity protein SCRIB and the spindle positioning determinant
LGN to link cell polarity and cell division orientation. Collectively, these
findings provide direct evidence for the existence of a hierarchy of
epithelial cell lineages during prostate development and tumorigenesis
and a novel mechanism by which E-cadherin acts an anchor to maintain
prostate epithelial division orientation and to prevent tumorigenesis in
vivo.
Biography
Wei Qiang Gao received his PhD from Columbia
University in 1989 and did his post-doctoral re-
search at Columbia University and Rockefeller
University. From 1993-2010, he was a Scientist
and Senior Scientist at Genentech, Inc.. He then
relocated to China to initiate his endowed chair
professorship in Shanghai. He has made import-
ant contributions to the fields of neuroscience,
stem cells and tumorigenesis. More recently, his
group focuses on “cancer research and cancer
stem cells”. Dr. Gao has published more than 80
papers as either corresponding or the first author,
including Nature, Cell, Science, Neuron, Nature
Neuroscience, Nature Communications, Gastro-
enterology, PNAS, J. Neurosci., StemCell Reports,
etc. and has been granted 48 US patents. He is a
scholar of national “Thousand-Talents Program”,
the Chief Scientist of 2 programprojects from the
Ministry of Science and Technology of China and
2 key grants from the National Natural Science
Foundation of China. He has served as a reviewer
for grant proposals of Wellcome Trust in UK, NIH
in US, and NSFC and 36 journals including Nature,
Nature Medicine, Nature Cell Biology, Nature
KEY REGULATORS OF
SYMMETRICAL AND
ASYMMETRICAL DIVISION
OF EPITHELIAL CELLS IN
PROSTATE DEVELOPMENT AND
TUMORIGENESIS
Wei Qiang Gao
Shanghai Jiao Tong University, China
Wei Qiang Gao, J Med Oncl Ther 2018, Volume 3