Eps15 homology domain 1 promotes the evolution of papillary thyroid cancer by regulating endocytotic recycling of epidermal growth factor receptor

Abstract

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, and it is often observed to overexpress epidermal growth factor receptor (EGFR). Previous research has indicated that EH domain-containing 1 (EHD1) is associated with EGFR-mediated endocytotic recycling in multiple tumor types. The objective of the present study was to determine the protein expression levels and clinical significance of EHD1, EGFR, caveolin-1 (CAV-1) and RAB11 family interacting protein 3 (RAB11FIP3) in PTC. PTC specimens were analyzed for EHD1, EGFR, CAV-1 and RAB11FIP3 expression via immunohistochemistry and western blotting. The associations between protein expression and clinicopathological features were assessed. EHD1, EGFR, CAV-1 and RAB11FIP3 expression levels were increased in human PTC. Additionally, the expression level of EHD1 protein was significantly associated with tumor size, lymph node metastasis and EGFR expression (P<0.05). CAV-1 was associated with tumor size and EGFR expression (P<0.05). EGFR was only associated with lymph node metastasis (P=0.027) and RAB11FIP3 was not associated with any clinicopathological characteristics. The correlations between EHD1 and EGFR (r=0.564, P<0.05), CAV-1 (r=0.865, P<0.01) and RAB11FIP3 (r=0.504, P<0.05) were statistically significant. Overall, EHD1, CAV-1 and RAB11FIP3, which are key proteins in endocytotic recycling, promote PTC tumorigenesis through the regulation of the transport of EGFR.

Keywords: EH domain-containing 1; RAB11 family interacting protein 3; caveolin-1; epidermal growth factor receptor; papillary thyroid cancer.

Figure 1.

Immunohistochemical analysis of protein expression in adjacent normal tissues and tumor tissues of papillary thyroid cancer (n=72). (A) Representative samples expressing high EHD1, EGFR, RAB11FIP3 and CAV-1 in tumor tissues relative to normal tissues. Representative samples of EHD1, EGFR, RAB11FIP3 and CAV-1 expression (brown color staining), as detected by immunohistochemistry in a pair of tumor tissues and adjacent normal tissues. (B) Compared with adjacent normal tissues, tumor tissues expressed significantly increased EHD1 (P<0.01), EGFR (P<0.01), CAV-1 (P<0.01) and RAB11FIP3 (P<0.01) expression. Fig. 1B was created from the data of Table II. ***P<0.001. EHD1, EH domain-containing 1; EGFR, epidermal growth factor receptor; RAB11FIP3, RAB11 family interacting protein 3; CAV-1, caveolin-1.

Figure 2.

A total of 30 paired tumor and adjacent normal tissues were analyzed for EHD1, EGFR and CAV-1 expression by western blotting. (A) Two representative paired tumor and normal tissues are shown. EHD1, EGFR and CAV-1 expression was normalized to the internal control GAPDH. (B) The mean relative expression in these tumor tissues was significantly higher than that in the paired non-tumorous tissues (P<0.01). Statistical analysis was performed using a t-test. Fig. 2B was made according to the data of Table V. **P<0.01. EHD1, EH domain-containing 1; EGFR, epidermal growth factor receptor; CAV-1, caveolin-1; T, tumor; N, normal; IOD, integrated optical density.