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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11th International Conference on
Journal of Medical Oncology and Therapeutics | Volume 3
Helen He Zhu, J Med Oncl Ther 2018, Volume 3
hTERThigh NUMB-/LOW STATE
ENRICHES A CASTRATION
RESISTANT PROSTATE CANCER
CELL SUBPOPULATION WITH
TUMOR INITIATING CAPACITY
Helen He Zhu1, 2
1Ren Ji Hospital, School of Medicine, China
2Shanghai Jiao Tong University, China
Castration resistant prostate cancer (CRPC) remains one of the most
deadly and incurable cancer types worldwide. Tumor cells in CRPC
patient samples display tremendous heterogeneity. Cancer stem cells
(CSCs) are proposed to be the driving force in cancer progression and
recurrence. Identificationof theCSCor prostatecancer cell sub-population
with greater castration resistance is a key to the development of targeted
anti-CRPC treatment strategies. We report that the hTERThigh PCa cells
exhibit CSC properties including stem cell associated gene expression
signature, long term tumor propagating capacity, and epithelial-to-
mensenchymal transition. hTERThigh CSC cells display distinct cell
divisionmodes and can undergo both symmetric division and asymmetric
division, as compared to hTERT-/low Pca cells. Numb, an evolutionarily
conserved cell fate determinant, tends to segregate into the more
differentiating daughter cell during symmetric division and asymmetric
division of hTERThigh CSC cells. Further investigation revealed that Numb
is down-regulated and negatively correlated with PCa advancement.
Functionally, Numb exerted an inhibitory role in xenograft prostate tumor
growth and CRPC development via suppression of Notch and Hedgehog
signaling. Through a Numb promoter based lentiviral reporter system,
we were able to separate Numb-/low Pca cells from Numbhigh cells.
Numb-/low PCa cells are smaller and quiescent, preferentially express
Notch and Hedgehog downstream and stem-cell-associated genes, and
are associated with greater resistance to androgen deprivation therapy.
Targeting Notch and Hedgehog signaling with inhibitors can effectively
deplete the Numb-/low castration resistant PCa cells. Collectively, these
findings provide novel insight into cellular and molecular mechanisms for
the development of advanced CRPC and to the development of effective
anti-CRPC treatment strategies.
Helen He Zhu received her Bachelor Degree
from Fudan University, China. She performed
her PhD study in Molecular Pathology at School
of Medicine, University of California-San Diego
and did her postdoctorate training in the Depart-
ment of Biology, University of California-San Di-
ego. In 2012, She relocated back to China and
started to work as an Associate Professor then
Professor in Ren Ji Stem Cell Research Center,
Ren Ji Hospital at School of Medicine, Shanghai
Jiao Tong University. Her current work focuses
on 1) adult tissue stem cells from hematopoi-
etic system and prostate in tissue development
and tumorigenesis. 2) roles of prostate cancer
stem cells in therapeutic resistance and tumor
metastasis. Her publication includes first au-
thor and corresponding author papers in Blood,
PNAS, Gastroenterology, Clinical Cancer Re-
search, Cancer Research and etc.
BIOGRAPHY