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EP001/#255  Knockdown of E-cadherin expression promote cervical cancer progression through EGFR signaling pathway
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  1. Gwan Hee Han1,
  2. Hee Yun2,
  3. Sunghoon Kim2,
  4. Hanbyoul Cho2 and
  5. Jae-Hoon Kim2
  1. 1Sanggye Paik Hospital, Inje University College of Medicine, Department of Obstetrics and Gynecology, Seoul, Korea, Republic of
  2. 2Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Department of Obstetrics and Gynecology, Seoul, Korea, Republic of

Abstract

Introduction The expression of E-cadherin, a crucial cell adhesion molecule, plays a significant role in the progression of various malignancy. However, the role of E-cadherin in cervical cancer has not been elucidated yet. Therefore, we aimed to investigate the expression of E-cadherin in cervical cancer patients and its association with the pERK signaling pathway.

Methods Immunohistochemical analyze E-cadherin and pERK were performed using tissue microarray of cervical cancers and normal cervical epithelial tissues and clinicopathologic variables were analyzed. Also the functional studies with cervical cancer cell lines were evaluated.

Results The expression of E-cadherin was significantly reduced from normal to cancer, and associated with FIGO stage. Furthermore, E-cadherin expression was negatively correlated with pERK expression in cervical cancers. The Keplan-Meier plots demonstrated that E-cadherin lowexpression was associated with poor DFS and OS, and pERK, overexpression was significantly associated with poor DFS and OS. The DFS and OS with expression of low E-cadherin/high pERK was compared with patients with others which revealed a significant difference in DFS and OS. The Cox proportional hazards model revealed that a low E-cadherin/high pERK expression was an independent prognostic factor with respect to overall survival (HR=8.48 [95% CI, 3.36 – 21.37, p<0.01]. In cervical cancer cell lines, the knock down of E-cadherins promoted proliferation in cervical cancer cells and loss of E-cadherin led to EGFR mobility, which may stimulate EGFR dimerization and further boost its activation.

Conclusion/Implications Low expression of E-cadherin or combined with pERK is an indicator of poor prognosis in cervical cancer, suggesting their potential utility as prognostic test in clinical assessment.

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