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SUMMARY:‘Cellular Plasticity in Cancer:  driving force and therapeutic t
 arget’ - Professor Thomas Brabletz\, Department of Experimental Medicine
 \, University Erlangen-Nuernberg
DTSTART:20180605T100000Z
DTEND:20180605T110000Z
UID:TALK105442@talks.cam.ac.uk
CONTACT:Mala Jayasundera
DESCRIPTION:*Abstract*:\n\nWe have shown\, that in particular tumor cells 
 at the invasive front undergo a partial epithelial-mesenchymal transition 
 (EMT) and aberrantly express EMT-associated transcription factors (EMT-TFs
 ). The amount of such cancer cells strongly correlates with metastasis for
 mation and poor clinical outcome in human cancers. Strikingly\, metastases
  show a mesenchymal-epithelial re-transition (MET) with a re-differentiate
 d phenotype\, indicating high cancer cell plasticity and supporting a regu
 latory role of the tumor environment. We described that the EMT-TF ZEB1 is
  a crucial determinant of cellular plasticity. At molecular level\, ZEB1 i
 s linked in a double negative feedback loop with the miR-200 family and mi
 R-203\, which are strong inducers of epithelial differentiation. Thus aber
 rant ZEB1 expression stabilizes EMT and stemness\, thereby promoting disse
 mination\, metastasis and drug resistance of cancer cells. We have validat
 ed the findings\, by showing that a depletion of ZEB1 in the KPC-mouse mod
 el of pancreatic cancer counteracts tumor cell plasticity and metastasis. 
 Moreover we detected that ZEB1 controls the Notch pathway and directly coo
 perates with the Hippo-pathway effector YAP in driving aggressive cancer t
 ypes. We determined epigenetic modifications conferred by ZEB1\, screened 
 for epigenetic drug to restore expression of its silenced target genes and
  to subsequently overcome therapy resistance. Despite their potent tumor-p
 romoting effects\, EMT-TFs are rarely mutated in cancer. This likely due t
 o the necessity for a transient expression and the associated plasticity o
 f cancer cells\, underscoring the important role of non-mutated genes in c
 ancer progression. \n\n
LOCATION:Sackler Lecture Theatre (Level 7)\, Cambridge Institute for Medic
 al Research
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