TACC3 promotes epithelial-mesenchymal transition (EMT) through the activation of PI3K/Akt and ERK signaling pathways.
Transforming acidic coiled-coil protein 3 (TACC3) is a member of the TACC family, essential for mitotic spindle dynamics and centrosome integrity during mitosis. Mounting evidence suggests that deregulation of TACC3 is associated with various types of human cancer. However, the molecular mechanisms by which TACC3 contributes to the development of cancer remain largely unknown. Here, we propose a novel mechanism by which TACC3 regulates epithelial-mesenchymal transition (EMT). By modulating the expression of TACC3, we found that overexpression of TACC3 leads to changes in cell morphology, proliferation, transforming capability, migratory/invasive behavior as well as the expression of EMT-related markers. Moreover, phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated protein kinases (ERKs) signaling pathways are critical for TACC3-mediated EMT process. Notably, depletion of TACC3 is sufficient to suppress EMT phenotype. Collectively, our findings identify TACC3 as a driver of tumorigenesis as well as an inducer of oncogenic EMT and highlight its overexpression as a potential therapeutic target for preventing EMT-associated tumor progression and invasion.
Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA.
Geun-Hyoung
GH
Ha
Jong-Sup
JS
Park
Eun-Kyoung Yim
EK
Breuer
D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism
C495270:CTNNB1 protein, human; D008869:Microtubule-Associated Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C120551:TACC3 protein, human; D051176:beta Catenin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases