The transcription elongation factor TCEA3 induces apoptosis in rhabdomyosarcoma.
Amino Acid Chloromethyl Ketones
/ pharmacology
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Caspase Inhibitors
/ pharmacology
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ drug effects
DNA Methylation
/ genetics
Dactinomycin
/ pharmacology
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Rhabdomyosarcoma
/ genetics
Transcriptional Elongation Factors
/ genetics
Up-Regulation
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
27 01 2020
27 01 2020
Historique:
received:
25
09
2019
accepted:
10
01
2020
revised:
09
01
2020
entrez:
29
1
2020
pubmed:
29
1
2020
medline:
2
10
2020
Statut:
epublish
Résumé
TCEA3 is one of three genes representing the transcription elongation factor TFIIS family in vertebrates. TCEA3 is upregulated during skeletal muscle differentiation and acts to promote muscle specific gene expression during myogenesis. Rhabdomyosarcoma (RMS) is a pediatric cancer derived from the muscle lineage, but the expression or function of TCEA3 in RMS was uncharacterized. We found that TCEA3 expression was strongly inhibited in RMS cell lines representing both ERMS and ARMS subtypes of RMS. TCEA3 expression correlates with DNA methylation and we show that TBX2 is also involved in the repression of TCEA3 in RMS cell lines. Ectopic expression of TCEA3 inhibited proliferation of RMS cell lines and initiated apoptosis through both the intrinsic and extrinsic pathways. We found that only pan-caspase inhibitors could block apoptosis in the presence of TCEA3. While expression of TCEA3 is highest in skeletal muscle, expression has been detected in other tissues as well, including breast, ovarian and prostate. We found that ectopic expression of TCEA3 also promotes apoptosis in HeLa, MCF7, MDA-231, and PC3 cell lines, representing cervical, breast, and prostate cancer, respectively. Restoration of TCEA3 expression in RMS cell lines enhanced sensitivity to chemotherapeutic drugs, including TRAIL. Thus, TCEA3 presents a novel target for therapeutic strategies to promote apoptosis and enhance sensitivity to current chemotherapeutic drugs.
Identifiants
pubmed: 31988307
doi: 10.1038/s41419-020-2258-x
pii: 10.1038/s41419-020-2258-x
pmc: PMC6985194
doi:
Substances chimiques
Amino Acid Chloromethyl Ketones
0
Antineoplastic Agents
0
Caspase Inhibitors
0
Transcriptional Elongation Factors
0
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
0
transcription factor S-II
0
Dactinomycin
1CC1JFE158
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
67Subventions
Organisme : NIAMS NIH HHS
ID : R15 AR068622
Pays : United States
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