Publikation

Alternative splicing of Apoptosis Stimulating Protein of TP53-2 (ASPP2) results in an oncogenic isoform promoting migration and therapy resistance in soft tissue sarcoma (STS).

Wissenschaftlicher Artikel/Review - 02.07.2022

Bereiche
PubMed
DOI
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Zitation
Tsintari V, Walter B, Fend F, Overkamp M, Rothermundt C, Lopez C, Schittenhelm M, Kampa-Schittenhelm K. Alternative splicing of Apoptosis Stimulating Protein of TP53-2 (ASPP2) results in an oncogenic isoform promoting migration and therapy resistance in soft tissue sarcoma (STS). BMC cancer 2022; 22:725.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
BMC cancer 2022; 22
Veröffentlichungsdatum
02.07.2022
eISSN (Online)
1471-2407
Seiten
725
Kurzbeschreibung/Zielsetzung

Metastatic soft tissue sarcoma (STS) are a heterogeneous group of malignancies which are not curable with chemotherapy alone. Therefore, understanding the molecular mechanisms of sarcomagenesis and therapy resistance remains a critical clinical need. ASPP2 is a tumor suppressor, that functions through both p53-dependent and p53-independent mechanisms. We recently described a dominant-negative ASPP2 isoform (ASPP2κ), that is overexpressed in human leukemias to promote therapy resistance. However, ASPP2κ  has never been studied in STS.  MATERIALS AND METHODS: Expression of ASPP2κ was quantified in human rhabdomyosarcoma tumors using immunohistochemistry and qRT-PCR from formalin-fixed paraffin-embedded (FFPE) and snap-frozen tissue. To study the functional role of ASPP2κ in rhabdomyosarcoma, isogenic cell lines were generated by lentiviral transduction with short RNA hairpins to silence ASPP2κ expression. These engineered cell lines were used to assess the consequences of ASPP2κ silencing on cellular proliferation, migration and sensitivity to damage-induced apoptosis. Statistical analyses were performed using Student's t-test and 2-way ANOVA.