William T. Beck - Keynote Speaker - Cancer Research 2018

Biography:

William T. Beck, PhD, is University Distinguished Professor and former Head of the
Department of Biopharmaceutical Sciences in the College of Pharmacy at the
University of Illinois at Chicago. His research efforts have focused on understanding
the molecular and genetic mechanisms of anticancer drug action and tumor cell
resistance to anticancer drugs. His current research focuses on splicing factor genes
and their involvement in cancer initiation, progression, and resistance to therapy, as
well as their potential as novel therapeutic targets in ovarian, breast, and brain
cancers.Abstract: Pre‐mRNA splicing, mediated by splicing factors, is a normal
biochemical phenomenon that accounts in large part for the
proteomic diversity in our cells, as there are ~25,000 genes
but ~100,000 proteins. Splice “isoforms” are specific for:
tissue, disease, population, individuals, and are related to
drug response. Cancer‐specific alternative splicing as well as
aberrant expression of splicing factors is seen in tumors
compared to normal tissues, but the mechanistic basis for
this differential expression remains unclear. We found that
increased splicing in ovarian and breast cancer cells is
related to increased expression of some splicing factors,
including the heterogeneous nuclear ribonucleoprotein,
polypyrimidine tract binding protein 1 (PTBP1), and the
serine‐arginine rich protein, SRp20/SRSF3. Inhibition of
expression of PTBP1 inhibits in vitro tumor cell growth,
colony formation, invasiveness (metastatic behavior),
aerobic glycolysis (Warburg effect), and tumor growth in
vivo; alters expression of >1500 genes in many metabolic
pathways; and sensitizes cells to drugs. SRSF3 is upregulated
in breast tumor tissues compared to normal breast tissue,
and correlated with tumor grade. In addition, knockdown of
SRp20 resulted in cell growth inhibition and apoptosis in a
dose‐dependent manner, and was partially reversed by pretreating
the cells with the pan‐caspase inhibitor z‐VAD‐fmk,
suggesting partial involvement of caspases in this apoptosis.
Finally, we have identified by high‐throughput screening an
FDA‐approved small molecule inhibitor of PTBP1 that
inhibits cancer cell growth. Future studies will be discussed.

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