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Allied Journal of Medical Research
|
Volume 2
Page 25
Note:
allied
academies
CANCER THERAPY AND ONCOLOGY
NEUROLOGY AND BRAIN DISORDERS
&
International Conference on
International Conference on
J u n e 2 1 - 2 2 , 2 0 1 8 | O s a k a , J a p a n
Joint Event on
THERAPEUTIC TARGETING OF TFF3
INHIBITS ONCOGENESIS IN COLORECTAL
CANCER
Rumei Chen, Qingyun Chong, Vijay Pandey, Mengyi Zhang,
Basappa Salundi, Alan Prem Kumar
and
Peter Edward Lobie
National University of Singapore, Singapore
T
refoil Factor 3 (TFF3) expression was observed to be upregulated in
colorectal cancer (CRC) and correlated with distant metastasis and
poor survival outcomes. The present study investigates the functional
role of TFF3 and explores the potential of therapeutic inhibition of TFF3
in CRC alone and in combination with conventional chemotherapy.
We demonstrated that the forced expression of TFF3 increased cell
viability of CRC cells, being attributed to increased cell cycle S-phase
entry and decreased apoptosis. Furthermore, the forced expression of
TFF3 enhanced the capacity for foci formation and promoted the cancer
stem cell-like behaviour of CRC cells. In contrast, the siRNA-mediated
depletion of TFF3 decreased the oncogenicity of CRC cells as indicated
by the above parameters. Furthermore, AMPC, a novel and selective
small molecule inhibitor of TFF3, has been developed in our laboratory
and is used to examine the functional implications of TFF3 inhibition in
CRC cells. Consistently, AMPC inhibition of TFF3 in CRC cells resulted in
reduction of oncogenic properties. Mechanistically, we demonstrate that
the TFF3-stimulated oncogenic behavior of CRC cells is dependent on
TFF3 activation of the MAPK/ERK pathway. Besides showing efficacy as
a single agent, AMPC when used in combination with 5-fluorouracil (5-FU)
exhibited a synergistic inhibitory effect, consistent with our observation
that TFF3 depletion increased 5-FU sensitivity in CRC cells. In summary,
our study highlights the potential of TFF3 as a therapeutic target in CRC
and underscores the potential benefits of its pharmacological inhibition
in this cancer using AMPC.
Rumei Chen received her BSc with academic
excellence scholarship from Nan Kai Universi-
ty, China. Upon graduation, she was conferred
a full-time PhD research scholarship offered
by the Yong Loo Lin School of Medicine in Na-
tional University of Singapore, Singapore. Her
research focus revolves around the profiling
of an estrogen-regulated oncogene (TFF3) in
CRC and the development of novel therapeutic
strategies against it. Meanwhile she has been
accredited by Experimental Therapeutics Cen-
tre & D3 in Singapore during a course that edu-
cates scientists about conducting translational
R&D theory and practice. Fromwhich, she learnt
many practical guidance to translate basic re-
search findings into full-fledged R&D projects.
Other than research, she has been active in pro-
moting science-related events such as assisting
to organize the International Union of Basic and
Clinical Pharmacology world conference. She is
a member of many international committees,
such as European Association for Cancer Re-
search, Pharmacological Society of Singapore.
chenrumei@u.nus.eduBIOGRAPHY
Rumei Chen et al., Allied J Med Res 2018, Volume 2