XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
33.
TraIL-INDUCED aPOPTOSIS caUSES aCTIvaTION of pro-SUrvival
paTHWaYS IN NON-aDHErENTLY grOWING COLON caNCEr CELLS
Lenka Kočí, Martina Hýžďalová, Alena Vaculová,
Jiřina Hofmanová and Alois Kozubík
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech
Republic, v.v.i., Kralovopolska 135, Brno 61265, Czech republic
Resistance of transformed epithelial cells to the deachment-induced apoptosis (anoikis)
promotes cancer cell invasion and metastasis. We studied the effects of TNF-related
apoptosis inducing ligand (TRAIL) on cytokinetic parameters and adhesive properties of
the cell lines derived from human foetal (FHC cells) and human adenocarcinoma (HT-29
cells) colon tissues in association with anoikis induction.
We detected the significant decrease of TRAIL-induced apoptosis in the non-adherently
growing HT-29 cells in comparison with the adherent cultivation. Based on this finding we
focused our attention to detail mechanisms of the cell survival under TRAIL treatment.
We confirmed our hypothesis of activation of pro-survival pathways, actually PI3K/Akt
and MAPK/ERK, which are connected with focal adhesion kinase (FAK) phosphorylation.
Increased phosphorylation of Akt and ERK kinases and also enhanced expression of FLIP
and Mcl-1 proteins as downstream molecules of PI3K/Akt pathway were observed during
non-adherent cultivation.
Taken together, our data suggested that the decrease of the TRAIL-mediated apoptosis
of colon epithelial cells induced by non-adherent type of cultivation is connected with
activation of pro-survival pathways.
Acknowledgements: This work was supported by grants 305/09/1526 GACR, 303/09/
H048 GACR, and 524/07/1178 GACR.
XXII. Biochemistry Congress, Martin
151