|Start Date / Time||November 7, 2018 at 9:00 AM|
|End Date / Time||November 7, 2018 at 10:00 AM|
|Location||9455 MRB IV|
|Presenter Name||Eunyoung Choi, Ph.D.|
|Presentation Title||Heterogeneity and dynamics of active Kras-induced pre-neoplastic lineages from mouse stomach|
|Status||This meeting has already occurred|
Cellular heterogeneity in stem cell populations is considered a source for cancer cell generation. However, the cellular or phenotypic heterogeneity and mechanisms of pre-neoplasia progression in stomach metaplasia has not been elucidated. My lab has established novel metaplastic and pre-neoplastic organoid lines derived from Mist1-Kras(G12D) mouse stomachs. We investigated functional roles for Kras activation and cellular heterogeneity in metaplasia progression. The pre-neoplastic organoids displayed more aggressive behaviors with cortactin expression at invasive lamellipodia and we identified two pre-neoplastic stem cell (PNSC) populations in pre-neoplastic cells, either dormant or proliferative, exhibiting stemness potential. The organoids died or showed altered cellular behaviors and diminished aggressiveness in response to inhibition of MEK, a downstream mediator of Kras signaling. However, the organoids surviving after MEK inhibitor treatment maintained cellular heterogeneity. In conclusion, oncogenic Kras controls cellular dynamics and progression of metaplasia and PNSCs might be the source for maintenance of heterogeneity in pre-neoplasia.