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Published on: October 27, 2020
TACC3 is essential for EGF-mediated EMT in cervical cancer
Geun-Hyoung Ha1, Jung-Lye Kim, Eun-Kyoung Breuer
1Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
Abstract:
The third member of transforming acidic coiled-coil protein (TACC) family, TACC3, has been shown to be an important player in the regulation of centrosome/microtubule dynamics during mitosis and found to be deregulated in a variety of human malignancies. Our previous studies have suggested that TACC3 may be involved in cervical cancer progression and chemoresistance, and its overexpression can induce epithelial-mesenchymal transition (EMT) by activating the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated protein kinases (ERKs) signal transduction pathways. However, the upstream mechanisms of TACC3-mediated EMT and its functional/clinical importance in human cervical cancer remain elusive. Epidermal growth factor (EGF) has been shown to be a potent inducer of EMT in cervical cancer and associated with tumor invasion and metastasis. In this study, we found that TACC3 is overexpressed in cervical cancer and can be induced upon EGF stimulation. The induction of TACC3 by EGF is dependent on the tyrosine kinase activity of the EGF receptor (EGFR). Intriguingly, depletion of TACC3 abolishes EGF-mediated EMT, suggesting that TACC3 is required for EGF/EGFR-driven EMT process. Moreover, Snail, a key player in EGF-mediated EMT, is found to be correlated with the expression of TACC3 in cervical cancer. Collectively, our study highlights a novel function for TACC3 in EGF-mediated EMT process and suggests that targeting of TACC3 may be an attractive strategy to treat cervical cancers driven by EGF/EGFR signaling pathways.
Insights
Transforming acidic coiled-coil protein 3 (TACC3) drives epithelial-mesenchymal transition (EMT) in cervical cancer. Targeting TACC3 may offer a new strategy for treating cancers driven by epidermal growth factor receptor (EGFR) signaling.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Transforming acidic coiled-coil protein 3 (TACC3) is implicated in mitosis and deregulated in human cancers.
- Previous research suggests TACC3's role in cervical cancer progression and chemoresistance, potentially inducing epithelial-mesenchymal transition (EMT) via PI3K/Akt and ERK pathways.
- The upstream regulation and specific function of TACC3 in cervical cancer-associated EMT remain unclear.
Purpose of the Study:
- To investigate the upstream mechanisms regulating TACC3 in cervical cancer.
- To elucidate the role of TACC3 in epidermal growth factor (EGF)-induced EMT in cervical cancer.
- To assess the functional and clinical significance of TACC3 in cervical cancer progression.
Main Methods:
- Analyzed TACC3 expression in cervical cancer tissues.
- Investigated TACC3 induction by EGF and its dependence on EGF receptor (EGFR) tyrosine kinase activity.
- Utilized TACC3 depletion (e.g., siRNA) to assess its necessity in EGF-mediated EMT.
- Examined the correlation between TACC3 and Snail expression in cervical cancer.
Main Results:
- TACC3 is overexpressed in cervical cancer and its expression is induced by EGF in an EGFR-dependent manner.
- Depletion of TACC3 abrogates EGF-induced EMT, establishing TACC3 as a requirement for this process.
- TACC3 expression positively correlates with Snail, a key EMT regulator, in cervical cancer specimens.
Conclusions:
- TACC3 plays a critical role in mediating EGF/EGFR-driven EMT in cervical cancer.
- TACC3 is a novel functional component in the EGF-induced EMT pathway.
- Targeting TACC3 presents a potential therapeutic strategy for cervical cancers associated with EGF/EGFR signaling.
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