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Hedgehog signaling negatively co-regulates BH3-only protein Noxa and TAp73 in TP53-mutated cells
In the present study, we show that pharmacological repression by the Hedgehog (Hh) pathway inhibitor (HPI) GANT61 induces expression of the proapoptotic protein Noxa in TP53-mutated embryonal pediatric tumor cells driven by Hh signaling (i.e. rhabdomyosarcoma (RMS) and medulloblastoma (MB)). Similarly, genetic silencing of Gli1 by siRNA causes increased Noxa mRNA and protein levels, while overexpression of Gli1 results in decreased Noxa expression. Furthermore, TAp73 mRNA and protein levels are increased upon Gli1 knockdown, while Gli1 overexpression reduces TAp73 mRNA and protein levels.
Source: Cancer Letters - April 24, 2018 Category: Cancer & Oncology Authors: Michael Torsten Meister, Cathinka Boedicker, Thomas Klingebiel, Simone Fulda Tags: Original Articles Source Type: research