Analysis of the epidermal growth factor receptor/phosphoinositide‐dependent protein kinase‐1 axis in tumor of the external auditory canal in response to epidermal growth factor stimulation. Issue 3 (30th March 2022)

• Record Type: Journal Article
• Authors: Akiyama, Naotaro; Yamamoto‐Fukuda, Tomomi; Yoshikawa, Mamoru; Kojima, Hiromi
• Is Part Of: Laryngoscope investigative otolaryngology. Volume 7:Issue 3(2022)
• Page Start: 730
• Page End: 739
• Publication Date: 2022-03-30
• Subjects: EGFR -- external auditory canal squamous cell carcinoma -- PDPK1; Otolaryngology -- Periodicals; Laryngoscopy -- Periodicals; Otolaryngology; Otolaryngology; Periodicals; Periodicals; 617.51
• DOI: 10.1002/lio2.785
• Languages: English
• ISSNs: 2378-8038

Abstract

Abstract: Objectives: The epidermal growth factor receptor (EGFR) is related to the invasion and metastasis of external auditory canal (EAC) squamous cell carcinoma (SCC). The phosphoinositide‐dependent protein kinase‐1 (PDPK1) accelerates tumor cell growth through anti‐apoptotic signaling under the influence of downstream EGFR‐mediated signaling pathways. In this study, we investigated the EGFR/PDPK1 axis in the EAC under EGF stimulation. Methods: We confirmed EGFR and PDPK1 expression in human EACSCC specimens immunohistochemically. We next transfected the EGF expression vector in the mouse EAC and then conducted a PDPK1 inhibitory experiment. Immunohistochemical analysis was performed in the mouse EAC, using anti‐EGF, anti‐EGFR, anti‐PDPK1, and anti‐Ki67 antibodies. Immunohistochemical analysis of cleaved caspase‐3 and terminal deoxy(d)‐UTP nick end labeling (TUNEL) detection assays were also performed for the assessment of apoptosis in the inhibitory experiment. Results: Immunohistochemical analysis revealed overexpression and colocalization of EGFR and PDPK1 in human EACSCC specimens. The growth of a protuberant tumor was observed in the mouse EAC in which EGF expression vector was transfected, and EGF, EGFR, PDPK1, and Ki67 labeling indexes (LIs) were significantly increased. PDPK1 inhibition then induced normal epithelial appearance in the EAC. Moreover, EGF, EGFR, PDPK1, and Ki67 LIs were decreased, and cleaved caspase‐3 and TUNEL LIs were increased in the EAC. Conclusion: We demonstrated the possibility that PDPK1 plays an important role in EACSCC. Level of Evidence: NA.