Informace o publikaci

TUSC3 loss enhances ovarian cancer malignancy by promoting the ER stress response



Rok publikování 2015
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Lékařská fakulta

Popis Ovarian cancer (OC) is one of the most serious cancers in women and despite recent progress in diagnosis and therapy, the prognosis for patients with OC is unfavorable, mostly because of late diagnosis and lack of reliable prognostic and predictive biomarkers. Recently, we described that epigenetic silencing of TUSC3 correlates with poor overall and disease-free survival of OC patients. TUSC3 is a putative tumor suppressor located in the membrane of endoplasmic reticulum (ER) participating in protein N-glycosylation. It is well established, that disturbances in N-glycosylation are associated with cancer development, however, the precise molecular mechanism, including the role of TUSC3, remains unclear. In our model, TUSC3 loss enhanced growth of OC cells in mice confirming the status of TUSC3 as a tumor suppressor, moreover, it altered ER stress response and promoted epithelial-to-mesenchymal transition in OC cells. In addition, TUSC3 downregulation resulted in earlier formation of 3D spheroids under low-adhesion condition and provided resistance to N-glycosylation inhibition-induced decomposition of spheroids. We conclude, that the cumulative effect of TUSC3 silencing and extrinsic signals triggering the ER stress response contributes to EMT and tumor dissemination as well as tumor progression in OC.
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