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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
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Page 75
CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11th International Conference on
Journal of Medical Oncology and Therapeutics | Volume 3
INCREASING TELOMERASE
IN HUMAN CANCER
STEM CELLS BY NOVEL
COMPOUNDS ENHANCED
THE SENSITIVITY OF THE
CELLS TO CERTAIN ANTI-
CANCER AGENTS
E Priel, T Golochovsky, J Gopas and M Elkabetz
Ben-Gurion University of the Negev, Israel
Telomerase, a ribonucleoprotein is responsible for the
re-elongation of telomeres and is not or is slightly
expressed in somatic cells but it is highly expressed
in most of the tumor cells. Telomerase expression
is regulated by various factors and recently it was
suggested that some mRNA splice variants for human
telomerase catalytic subunit (hTERT) regulate the activity
of telomerase. The expression of telomerase in cancer
stem cells was previously reported but the regulation of
its expression and activity in cancer stem cells was not
thoroughly investigated. Here we show that the hTERT
dominant negative splice variant beta is highly expressed
in both the adherent and the mammospheres (cancer
stem cells) of human breast cancer cell line (MCF7). We
found that telomerase activity in cancer stem cells is also
regulated by the relative expressions of the full length and
the betta splice variants of TERT. We synthesized novel
compounds (AGS) that activate telomerase expression in
various human and animal cells as well as, in vivo, in animal
models. Treating cancer stem cells with these compounds
increased the expression of the full length TERT relatively
to the beta splice variant. Pretreatment of cancer stem cells
with the telomerase increasing compound increase the
sensitivity of these cells to anti- cancer agents in general
and specifically to topoisomerase inhibitors. The results of
this study suggest a novel approach, based on telomerase
activation, for increasing the sensitivity of cancer stem
cells to chemotherapeutic agents.
J Med Oncl Ther 2018, Volume 3
EGFR SORTING IN LUNG
CANCER: “SMELLS LIKE
A SORTILIN SPIRIT”
T Naves, H Al-Akhrass, F Vincent and F Lalloué
Université de Limoges, France
The aim of the present project is to obtain a better
understanding of EGFR deactivation in lung cancer. To
accomplish this we investigated the role of sortilin in EGFR
regulation following EGF-induced EGFR internalization.
The study also provides evidence that sortilin expression
represents a favorable prognostic marker in lung
adenocarcinoma patients.
Tyrosine kinase receptors such as the epidermal growth
factor receptor (EGFR) transduce information from the
microenvironment into the cell and activate homeostatic
signaling pathways. Internalization and degradation of
EGFR after ligand binding limits the intensity of proliferative
signaling, thereby helping to maintain cell integrity. In
cancer cells, deregulation of EGFR trafficking has a variety
of effects on tumor progression. Here we report that sortilin
is a key regulator of EGFR internalization. Loss of sortilin
in tumor cells promoted cell proliferation by sustaining
EGFR signaling at the cell surface, ultimately accelerating
tumor growth. In lung cancer patients, sortilin expression
decreased with increased pathologic grade, and expression
of sortilin was strongly correlated with survival, especially
in patients with high EGFR expression. Sortilin is therefore
a regulator of EGFR intracellular trafficking that promotes
receptor internalization and limits signaling, which in turn
impacts tumor growth.