TACC3 is essential for EGF-mediated EMT in cervical cancer.

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.

Transforming acidic coiled-coil proteins (TACCs) in human cancer.

Fine-tuned regulation of the centrosome/microtubule dynamics during mitosis is essential for faithful cell division. Thus, it is not surprising that deregulations in this dynamic network can contribute to genomic instability and tumorigenesis. Indeed, centrosome loss or amplification, spindle multipolarity and aneuploidy are often found in a majority of human malignancies, suggesting that defects in centrosome and associated microtubules may be directly or indirectly linked to cancer. Therefore, future research to identify and characterize genes required for the normal centrosome function and microtubule dynamics may help us gain insight into the complexity of cancer, and further provide new avenues for prognostic, diagnostics and therapeutic interventions. Members of the transforming acidic coiled-coil proteins (TACCs) family are emerging as important players of centrosome and microtubule-associated functions. Growing evidence indicates that TACCs are involved in the progression of certain solid tumors. Here, we will discuss our current understanding of the biological function of TACCs, their relevance to human cancer and possible implications for cancer management.

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.

Mitotic Kinases and p53 Signaling.

Mitosis is tightly regulated and any errors in this process often lead to aneuploidy, genomic instability, and tumorigenesis. Deregulation of mitotic kinases is significantly associated with improper cell division and aneuploidy. Because of their importance during mitosis and the relevance to cancer, mitotic kinase signaling has been extensively studied over the past few decades and, as a result, several mitotic kinase inhibitors have been developed. Despite promising preclinical results, targeting mitotic kinases for cancer therapy faces numerous challenges, including safety and patient selection issues. Therefore, there is an urgent need to better understand the molecular mechanisms underlying mitotic kinase signaling and its interactive network. Increasing evidence suggests that tumor suppressor p53 functions at the center of the mitotic kinase signaling network. In response to mitotic spindle damage, multiple mitotic kinases phosphorylate p53 to either activate or deactivate p53-mediated signaling. p53 can also regulate the expression and function of mitotic kinases, suggesting the existence of a network of mutual regulation, which can be positive or negative, between mitotic kinases and p53 signaling. Therefore, deciphering this regulatory network will provide knowledge to overcome current limitations of targeting mitotic kinases and further improve the results of targeted therapy.

The Role of Proteomics in the Diagnosis and Treatment of Women's Cancers: Current Trends in Technology and Future Opportunities.

Technological and scientific innovations over the last decade have greatly contributed to improved diagnostics, predictive models, and prognosis among cancers affecting women. In fact, an explosion of information in these areas has almost assured future generations that outcomes in cancer will continue to improve. Herein we discuss the current status of breast, cervical, and ovarian cancers as it relates to screening, disease diagnosis, and treatment options. Among the differences in these cancers, it is striking that breast cancer has multiple predictive tests based upon tumor biomarkers and sophisticated, individualized options for prescription therapeutics while ovarian cancer lacks these tools. In addition, cervical cancer leads the way in innovative, cancer-preventative vaccines and multiple screening options to prevent disease progression. For each of these malignancies, emerging proteomic technologies based upon mass spectrometry, stable isotope labeling with amino acids, high-throughput ELISA, tissue or protein microarray techniques, and click chemistry in the pursuit of activity-based profiling can pioneer the next generation of discovery. We will discuss six of the latest techniques to understand proteomics in cancer and highlight research utilizing these techniques with the goal of improvement in the management of women's cancers.