In vivo administration of RITA or GANT61 suppressed rhabdomyosarcoma xenograft growth in nude mice; however, co-administration did not further enhance tumor suppression, even though cell proliferation was decreased.
In addition, we found that in rhabdomyosarcoma and leiomyosarcoma tumors the expression of ZNF281/Zfp281 is significantly higher compared with normal counterparts.
We demonstrate that oncogenic RAS, acting through the RAF-MEK [mitogen-activated protein kinase (MAPK) kinase]-ERK (extracellular signal-regulated kinase) MAPK effector pathway, inhibits myogenic differentiation in rhabdomyosarcoma by repressing the expression of the prodifferentiation myogenic transcription factor, MYOG.
ZBTB16 effectively differentiates PNETs from other small round blue cell tumor mimics, including the two most common germ cell tumor-derived somatic malignancies - rhabdomyosarcoma and nephroblastoma.
Constitutively active YAP functioned as an early genetic lesion, permitting bypass of senescence and priming myoblasts to tolerate subsequent expression of hTERT and oncogenic Ras, which were necessary and sufficient to generate murine xenograft tumors mimicking RMS in vivo.
Reciprocally, YAP transcriptionally upregulates the Notch ligand genes <i>JAG1</i> and <i>DLL1</i> and the core Notch transcription factor <i>RBPJ</i> This bidirectional circuit boosts expression of key stem cell genes, including <i>SOX2</i>, which is functionally required for eRMS spheres.
This revealed that only 20% of the up or downregulated genes are identical, suggesting substantial differences in gene expression between YAP and KRAS-driven rhabdomyosarcomas.
In the present study, we showed that overexpression of XAB2 inhibited ATRA-induced cellular differentiation in human rhabdomyosarcoma cell line, and that knockdown of XAB2 by small interfering RNA (siRNA) increased ATRA-sensitive cellular differentiation in the human promyelocytic leukemia cell line HL60 at both physiologic (10(-9)-10(-8) mol/L) and therapeutic (10(-7) mol/L) concentrations of ATRA.
Among neoplastic tissues, WT1 has been documented in the cytoplasm of benign and malignant vascular tumors and in rhabdomyosarcoma, while there are no available studies about its expression in myofibroblastic tumors.
To investigate whether canonical β-catenin signaling in RMS is involved in differentiation and aggressiveness of RMS, we analyzed the effects of WNT3A and of a siRNA-mediated or pharmacologically induced β-catenin knock-down on proliferation, apoptosis and differentiation of embryonal and alveolar RMS cell lines.
Identification of the Wnt2 gene and its overexpression in ERMS cells was confirmed in human rhabdomyosarcoma cell lines and prompted further analysis of the Wnt signaling pathway.
The expressions of Akt, phosphorylated Akt Ser473, phosphorylated Akt Thr308, phosphorylated nuclear factor-kappa b p65 Ser536, and Bcl-2 significantly decreased; however, the expressions of phosphorylated glycogen synthase kinase-3beta Ser9, phosphorylated forkhead in human rhabdomyosarcoma Ser256, and phosphorylated caspase-9 Ser196 increased in response to lactoferrin treatment in SGC-7901.
We identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma orthotopic patient-derived xenografts tumours in vivo.
Comprehensive preclinical testing revealed that targeting the WEE1 kinase in the G<sub>2</sub>/M pathway is the most effective approach in vivo for high-risk RMS.
This study demonstrates that in addition to IMT, abnormalities of ALK1 and p80 expression with a variety of structural chromosomal changes are found in several sarcomas, especially rhabdomyosarcoma and malignant peripheral nerve sheath tumor.
The infectious entry of HEV71 into rhabdomyosarcoma cells was shown to be significantly inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis (CME) that include AP2A1, ARRB1, CLTC, CLTCL1, SYNJ1, ARPC5, PAK1, ROCK1, and WASF1.
EV-A71-289A and EV-A71-289T were used to infect human rhabdomyosarcoma cells, control human brain microvascular endothelial cells (HBMECs), and VIM-knockout (KO) HBMECs and inoculated BALB/c mice, SV129 mice, and VIM-KO SV129 mice.
In contrast to RD cells that expressed preferentially myoid and not neurofilament proteins (NFPs) upon treatment with UDP-4, differentiated RD/TE-671 cells exhibited characteristic dendritic processes and expressed NFPs (NFP68, NFP160, and NFP200), parvalbumin (calcium-binding protein), and neuron-specific enolase, as well as a small amount of vimentin and desmin.