TCEA3 binds to TGF-beta receptor I and induces Smad-independent, JNK-dependent apoptosis in ovarian cancer cells.
TFIIS is a transcription elongation factor conserved in frog, mouse and human. Recently, knockdown of TCEA1, the most well-characterized isoform of TFIIS, by RNA silencing was reported to inhibit cancer cell proliferation and induce apoptosis in breast, lung and pancreatic cancer cell lines through activation of p53 (Hubbard et al., 2008 [1]). However, the functions of other TFIIS isoforms are poorly defined. The present study shows that TCEA3, an isoform of TFIIS, can trigger ovarian cancer-specific cell death by activating the JNK signaling pathway. TCEA3 expression is low in ovarian cancer cell lines compared to noncancerous ovarian epithelial cells. Suppression of TCEA3 in noncancerous ovarian epithelial cells promotes cell growth whereas ectopic expression of TCEA3 in ovarian cancer cell lines induces the caspase-dependent mitochondrial cell death pathway. Molecular and chemical inhibition assays show that the interaction of TCEA3 with TGFβ receptor I induces cell death in ovarian cancer cell through Smad-independent activation of the JNK pathway. These results reveal that TCEA3 induces a novel apoptotic mechanism in OEC, which provides TCEA3 as a novel target to develop therapeutics of ovarian cancer.
Department of Biomedical Science, College of Life Science, CHA University, Seoul, Republic of Korea.
Young
Y
Cha
Dae-Kwan
DK
Kim
Jashil
J
Hyun
Seong-Jin
SJ
Kim
Kyung-Soon
KS
Park
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D035602:Transcriptional Elongation Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D035602:Transcriptional Elongation Factors; D016212:Transforming Growth Factor beta; C018648:transcription factor S-II; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D020169:Caspases