Akiyama Naotaro, Yamamoto-Fukuda Tomomi, Yoshikawa Mamoru, Kojima Hiromi
Department of Otorhinolaryngology Toho University School of Medicine Tokyo Japan.
Department of Otorhinolaryngology Jikei University School of Medicine Tokyo Japan.
Laryngoscope Investig Otolaryngol. 2022 Mar 30;7(3):730-739. doi: 10.1002/lio2.785. eCollection 2022 Jun.
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.
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.
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.
We demonstrated the possibility that PDPK1 plays an important role in EACSCC.Level of Evidence: NA.
表皮生长因子受体（EGFR）与外耳道（EAC）鳞状细胞癌（SCC）的侵袭和转移有关。磷酸肌醇依赖性蛋白激酶-1（PDPK1）在下游EGFR介导的信号通路影响下，通过抗凋亡信号加速肿瘤细胞生长。在本研究中，我们研究了在表皮生长因子（EGF）刺激下EAC中的EGFR/PDPK1轴。
我们通过免疫组织化学方法证实了人EAC SCC标本中EGFR和PDPK1的表达。接下来，我们在小鼠EAC中转染EGF表达载体，然后进行PDPK1抑制实验。使用抗EGF、抗EGFR、抗PDPK1和抗Ki67抗体对小鼠EAC进行免疫组织化学分析。在抑制实验中，还进行了裂解的半胱天冬酶-3的免疫组织化学分析和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）检测试验，以评估细胞凋亡情况。
免疫组织化学分析显示，在人EAC SCC标本中EGFR和PDPK1过表达且共定位。在转染了EGF表达载体的小鼠EAC中观察到突出肿瘤的生长，并且EGF、EGFR、PDPK1和Ki67标记指数（LIs）显著增加。然后，PDPK1抑制诱导EAC中出现正常上皮外观。此外，EAC中EGF、EGFR、PDPK1和Ki67 LIs降低，而裂解的半胱天冬酶-3和TUNEL LIs增加。
我们证明了PDPK1在EAC SCC中起重要作用的可能性。证据水平：无。
