Cancers, Vol. 12, Pages 1947: Characterization of mTOR Activity and Metabolic Profile in Pediatric Rhabdomyosarcoma

Cancers, Vol. 12, Pages 1947: Characterization of mTOR Activity and Metabolic Profile in Pediatric Rhabdomyosarcoma Cancers doi: 10.3390/cancers12071947 Authors: Luca Felkai Ildikó Krencz Dorottya Judit Kiss Noémi Nagy Gábor Petővári Titanilla Dankó Tamás Micsík András Khoor Tamás Tornóczky Zoltán Sápi Anna Sebestyén Monika Csóka mTOR activation has been observed in rhabdomyosarcoma (RMS); however, mTOR complex (mTORC) 1 inhibition has had limited success thus far. mTOR activation alters the metabolic pathways, which is linked to survival and metastasis. These pathways have not been thoroughly analyzed in RMSs. We performed immunohistochemistry on 65 samples to analyze the expression of mTOR complexes (pmTOR, pS6, Rictor), and several metabolic enzymes (phosphofructokinase, lactate dehydrogenase-A, β-F1-ATPase, glucose-6-phosphate dehydrogenase, glutaminase). RICTOR amplification, as a potential mechanism of Rictor overexpression, was analyzed by FISH and digital droplet PCR. In total, 64% of the studied primary samples showed mTOR activity with an mTORC2 dominance (82%). Chemotherapy did not cause any relevant change in mTOR activity. Elevated mTOR activity was associated with a worse prognosis in relapsed cases. RICTOR amplification was not confirmed in any of the cases. Our findings suggest the importance of the Warburg effect and the pentose-phosphate pathway beside a glutamine demand in RMS cells. The expression p...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research