Up-regulation of ITCH is associated with down-regulation of LATS1 during tumorigenesis and progression of cervical squamous cell carcinoma

Abstract

Purpose: The molecular basis for the normal cervical squamous epithelium advance to cervical intraepithelial neoplasia (CIN I, CIN II, CIN III) and ultimately to invasive carcinoma has not yet been defined. We explored the abnormal expression of ITCH (AIP4) and its degrading substrate Large Tumor Suppressor 1 (LATS1) in CINs and cervical cancers, which might disrupt the normal differentiation of the cervical epithelia and contribute to the tumorigenesis of the cervix. Methods: A series of 110 samples, comprising 24 cases of normal cervical tissues, 20 cases of CIN I, 26 cases of CIN II/III and 40 cases of squamous cancer of the cervix (SCC) were used for analysis. The expression of ITCH and LATS1 was assessed in the tissues by immunohistochemistry, and statistically analyzed by SPSS13.0. Results: The increased nuclear and cytoplasmic expression levels of ITCH and the low membrane expression of LATS1 were strongly associated with the malignant transformation of the cervical epithelium and the histological progression of SCC. Moreover, the high nuclear and cytoplasmic expression levels of ITCH were significantly correlated with clinical stage (P=0.036, P=0.003, respectively) and tumor size (P=0.046,P=0.039, respectively); the low membrane expression of LATS1 was significantly correlated with clinical stage (P=0.036)and tumor size (P=0.023). Both the nuclear and cytoplasmic expression levels of ITCH were inversely associated with the membrane expression of LATS1 in cervical tissues (P<0.001, P<0.001, respectively). Conclusions: ITCH up-regulation and LATS1 down-regulation were closely associated with tumorigenesis and progression of SCC; therefore, inhibiting the expression of ITCH may serve as a novel therapeutic strategy for impeding the progression of precancerous neoplasm to SCC.