Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC). Altered epidermal growth factor receptor (EGFR) levels can contribute to tumor metastasis and resistance to therapies. The epithelial-mesenchymal transition (EMT), by which epithelial cells acquire a mesenchymal and invasive phenotype, contributes significantly to tumor metastasis in OSCC, and EGFR signaling is known to promote this process. Microtubule inhibition therapies cause EGFR inactivation or increase the sensitivity to EGFR targeting drugs in various cancers including OSCC. In this study, using OSCC model, we show that loss of a microtubule/tubulin binding protein, centrosomal protein 4.1-associated protein (CPAP), which is critical for centriole biogenesis and normal functioning of centrosome, caused an increase in the EGFR levels and signaling and, enhanced the EMT features and invasiveness of OSCC cells. Further, depletion of CPAP increased the tumorigenicity of these cells in a xeno-transplant model. Importantly, CPAP loss-associated EMT features and invasiveness of multiple OSCC cells were attenuated upon depletion of EGFR in them. Overall, our novel observations suggest that in addition to its previously known regulatory role in centrosome biogenesis and function, CPAP plays an important role in suppressing EMT and tumorigenesis in OSCC by regulating EGFR homeostasis and signaling.

中文翻译：

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CPAP表达的丧失促进口腔癌细胞中持续的EGFR信号传导和上皮-间质转化

口腔鳞状细胞癌（OSCC）是最常见的头颈部鳞状细胞癌（HNSCC）类型。改变的表皮生长因子受体（EGFR）水平可导致肿瘤转移和对治疗的耐药性。上皮-间充质转化（EMT）使上皮细胞获得间充质和侵袭性表型，显着促进OSCC中的肿瘤转移，并且已知EGFR信号传导可促进此过程。在包括OSCC在内的各种癌症中，微管抑制疗法会导致EGFR失活或增加对EGFR靶向药物的敏感性。在这项研究中，我们使用OSCC模型显示了微管/微管蛋白结合蛋白，中心体蛋白4.1相关蛋白（CPAP）的丢失，这对于中心体生物发生和中心体的正常功能至关重要，导致EGFR水平和信号传导增加，并增强了OSC细胞的EMT功能和侵袭性。此外，在异种移植模型中，CPAP的消耗增加了这些细胞的致瘤性。重要的是，一旦其中的EGFR耗尽，与CPAP丢失相关的EMT功能和多个OSCC细胞的侵袭性就会减弱。总体而言，我们的新发现表明，除了先前已知的在中心体生物发生和功能中的调节作用外，CPAP还通过调节EGFR稳态和信号传导在OSCC抑制EMT和肿瘤发生中起重要作用。CPAP损失相关的EMT特征和多个OSCC细胞的侵袭性在其中EGFR耗尽后减弱。总体而言，我们的新发现表明，除了其先前在中心体生物发生和功能中的已知调节作用外，CPAP还通过调节EGFR稳态和信号传导在OSCC抑制EMT和肿瘤发生中起重要作用。CPAP损失相关的EMT特征和多个OSCC细胞的侵袭性在其中EGFR耗尽后减弱。总体而言，我们的新发现表明，除了其先前在中心体生物发生和功能中的已知调节作用外，CPAP还通过调节EGFR稳态和信号传导在OSCC抑制EMT和肿瘤发生中起重要作用。