CPAP also plays an important role in suppressing tumorigenesis in OSCC by facilitating EGFR homeostasis
Oncotarget published “Loss of CPAP Causes Persistent EGFR Signaling and Epithelial-Mesenchymal Junction in Oral Cancer,” which reported that not only the abnormal functions of microtubules and microtubule-organizing centers such as centrosomes lead to cancer, but also the malignant tissues that are characterized are characterized by aberrant centriolar features and amplified centrosomes.
In this study, the authors show that the loss of expression of a microtubule / tubulin-binding protein, the centrosomal protein 4.1-associated protein, which is critical for centriole biogenesis and the normal function of the centrosome, leads to an increase in EGFR levels and its Signaling performed and enhanced the EMT properties and invasiveness of OSCC cells.
In addition, the depletion of CPAP increased the tumorigenicity of these cells in a xeno-transplant model. Importantly, the CPAP loss-associated EMT characteristics and the invasiveness of several OSCC cells were attenuated after the degradation of EGFR in them.
On the other hand, they found that CPAP protein levels were higher in EGF-treated OSCC cells as well as oral cancer tissues, suggesting that the commonly reported deviant centriolar features of tumors may be a consequence, but not the cause, of tumor progression.
Overall, these new observations indicate that in addition to its well-known indispensable role in centrosome biogenesis, CPAP also plays an important role in suppressing tumorigenesis in OSCC by facilitating EGFR homeostasis.
Dr. Radhika Gudi and Dr. Chenthamarakshan Vasu of the Medical University of South Carolina said, “Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with more than 600,000 new patients diagnosed, and is associated with more than 300,000 deaths each year.”
EGFR is significantly altered in OSCC and its prolonged signal transmission is mitogenic, which drives the uncontrolled proliferation of tumor cells.
Despite these advances in understanding EGFR signaling, the regulatory mechanisms underlying EGFR signaling and their implications for cancer development, progression, and metastasis are not fully understood.
Recent studies have shown that inhibiting the microtubules causes EGFR inactivation or increases sensitivity to EGFR-targeting drugs in various cancers, including OSCC.
Microtubules and microtubule organizing centers have multiple roles in cellular functions, including homeostasis of cell signaling, cilia formation, cytoskeletal actin organization, and centrosome / centriole duplication and normal cell division.
Paradoxically, however, they not only show that EGFR signaling, which is known to contribute to EMT, upregulates cellular CPAP levels in OSCC cells, but also demonstrates higher CPAP protein levels in OSCC tumors.
The Gudi / Vasu research team concluded in their oncotarget research output that although EGF stimulation has previously been reported to confer stem cell-like properties, increased invasiveness, and tumorigenic properties, the molecular mechanisms that regulate the OSCC cells EGF-induced EMT and tumorigenicity were unknown.
Hence, this study begins to shed light on the molecular mechanisms by which centrosome / MTOC-associated proteins are involved in preventing tumor development.
However, future studies are needed to investigate the mechanism by which CPAP suppresses EGFR-dependent EMT and tumorigenesis.
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Correspondence– Radhika Gudi – [email protected] and Chenthamarakshan Vasu – [email protected]
keywords – Tumor development, epithelial-mesenchymal junction, oral squamous cell carcinoma, EGFR, CPAP
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