cancer-stem-cells-2018-keynote

2 / 8

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 16
In tumours, accumulation of chemoresistant cells that express high
levels of anti-apoptotic proteins such as BCL-XL is thought to result
from the counter selection of sensitive, low expresser clones during
progression and/or initial treatment. We herein show that BCL-XL
expression is selectively advantageous to cancer cell populations
even in the absence of pro-apoptotic pressure. In transformed human
mammary epithelial cells BCL-XL favours full activation of signalling
downstreamof constitutively active RAS with which it interacts in a BH4
dependent manner. Comparative proteomic analysis and functional
assays indicate that this is critical for RAS-induced expression of
stemness regulators and maintenance of a cancer initiating cell (CIC)
phenotype. Resistant cancer cells thus arise from a positive selection
driven by BCL-XL modulation of RAS-induced self-renewal, and during
which apoptotic resistance is not necessarily the directly selected trait.
Biography
Philippe Juin obtained his PhD degree in 1995 for
his work on mitochondrial assembly. During his
post-doc in the UK, he defined the mitochondrial
apoptotic pathway as one major intrinsic tumor
suppressor mechanism triggered by oncogene
deregulation. As an Associate Researcher at IN-
SERM, he led increasingly ambitious investiga-
tions of the regulation of the mitochondrial apop-
totic pathway by Bcl-2 family members in human
cancer cells and he created in 2012 an INSERM
team that specifically focusses on the role of this
pathway in stress adaptation and tumor escape.
This team gained international recognition for its
fundamental and translational research on the
regulation of therapeutic response and tumor
progression by BCL-2 family members (Nature
Rev. Cancer 2013, Cell Rep. 2016, EMBO Rep.
2018 in press). This teamcontributed to establish
that changes in mitochondrial apoptotic priming
are at the core of breast cancer cells response
to cytotoxic stress and treatments, being influ-
enced by oncogene signaling, tumor suppressor
pathways, therapy and tumor context. This team
recently established a new function of BCL-2
members, that contributes contributing to the
self renewal of breast cancer initiating cells, and
defined the molecular events involved (Nature
Comm., 2017).
BCL-XL DIRECTLY
MODULATES RAS
SIGNALLING TO FAVOUR
CANCER CELL STEMNESS
Philippe Juin
1Institute de Recherche en Santé de l’Université
de Nantes, France
2Institute de Cancérologie de l’Ouest, Saint
Herblain, France
Philippe Juin, J Med Oncl Ther 2018, Volume 3