Oncotarget

Research Papers:

Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer

Radhika R. Gudi _, Harinarayanan Janakiraman, Philip H. Howe, Viswanathan Palanisamy and Chenthamarakshan Vasu _

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Abstract

Radhika R. Gudi1, Harinarayanan Janakiraman2, Philip H. Howe2, Viswanathan Palanisamy2 and Chenthamarakshan Vasu1

1 Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA

2 Department of Biochemistry, Medical University of South Carolina, Charleston, South Carolina, USA

Correspondence to:

Radhika Gudi,email: gudi@musc.edu
Chenthamarakshan Vasu,email: vasu@musc.edu

Keywords: tumorigenesis; epithelial-mesenchymal transition; oral squamous cell carcinoma; EGFR; CPAP

Received: November 15, 2020     Accepted: March 22, 2021     Published: April 13, 2021

Copyright: © 2021 Gudi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Higher epidermal growth factor receptor (EGFR) signaling can contribute to tumor metastasis and resistance to therapies in oral squamous cell carcinoma (OSCC). EGFR signaling can promote epithelial-mesenchymal transition (EMT) in OSCC. EMT is a process by which epithelial cells acquire invasive properties and it can contribute to tumor metastasis. Not only do the abnormal functions of microtubule and microtubule-organizing centers (MTOC) such as centrosomes lead to cancers, but also the malignant tissues are characterized by aberrant centriolar features and amplified centrosomes. Microtubule inhibition therapies increase the sensitivity to EGFR targeting drugs in various cancers. In this study, we show that the loss of expression of a microtubule/tubulin binding protein, centrosomal protein 4.1-associated protein (CPAP), which is critical for centriole biogenesis and normal functioning of the centrosome, caused an increase in the EGFR levels and its signaling and, enhanced the EMT features and invasiveness of OSCC cells. Further, depletion of CPAP enhanced 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. On the other hand, we found that CPAP protein levels were higher in EGF treated OSCC cells as well as in oral cancer tissues, suggesting that the frequently reported aberrant centriolar features of tumors are potentially a consequence, but not the cause, of tumor progression. Overall, our novel observations show that, in addition to its known indispensable role in centrosome biogenesis, CPAP also plays a vital role in suppressing tumorigenesis in OSCC by facilitating EGFR homeostasis.


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