FTS (fused toes homolog) a novel oncoprotein involved in uterine cervical carcinogenesis and a potential diagnostic marker for cervical cancer

Abstract

The high incidence and fatality rate of uterine cervical cancer warrant effective diagnostic and therapeutic target identification for this disease. Here, we have found a novel oncoprotein FTS (Fused Toes Homolog), which is involved in cervical cancer pathogenesis. Immunohistochemical analysis of human cervical biopsy samples revealed that the expression of FTS is absent in normal cervical epithelium but progressively overexpressed in human cervical intraneoplastic lesions (CIN-I to CIN-III), this characteristic phenomenon put this protein, a potential diagnostic marker for the screening of early neoplastic changes of cervix. Using FTS-specific small hairpin RNA (shRNA) in cervical cancer cells, we determined a specific role for FTS protein in, cervical neoplasia. Targeted stable knock down of FTS in HeLa cells led to the growth inhibition, cell-cycle arrest, and apoptosis with concurrent increase in p21 protein. FTS effectively represses the p21 mRNA expression in dual luciferase assay which indicates that p21 is transcriptionally regulated by this oncoprotein which in turn affect the regular cell-cycle process and its components. Consistent with this we found a reciprocal association between these proteins in early cervical neoplastic tissues. These data unraveled the involvement of new oncoprotein FTS in cervical cancer which plays a central role in carcinogenesis. Targeted inhibition of FTS lead to the shutdown of key elemental characteristics of cervical cancer and could lead to an effective therapeutic strategy for cervical cancer.

Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer

“…Based on data from the Cancer Genome Atlas, homologous deletion of AKTIP occurs in multiple cancer lineages including breast (2%), ovary (0.9%), and prostate (1%), consistent with a tumor-suppressor role. However, the functional role of AKTIP could be tumor type-specific, since it has been proposed as a putative oncoprotein in cervical cancer but a tumor suppressor in ovarian cancer (Cinghu et al 2011;Notaridou et al 2011). INHBA encodes inhibin beta A, a subunit of both the activin and inhibin receptors of the transforming growth factor (TGF-beta) superfamily (Risbridger et al 2001).…”

EMT in cervical cancer: Its role in tumour progression and response to therapy

“…FTS expression is undetectable in normal epithelial cervical cells. Its expression positively correlates with the stage and grade of cervical cancer [45]. EGF treatment increases the phosphorylation of EGFR and ERK, leading to the accumulation of ATF2 in the nucleus [46].…”

“…FTS (Fused Toes Homolog) is an oncogene involved in cervical cancer pathogenesis [45]. FTS expression is undetectable in normal epithelial cervical cells.…”

Phosphorylation of threonine 190 is essential for nuclear localization and endocytosis of the FTS (Fused Toes Homolog) protein

“…It was found to interact with PKB and PDK when overexpressed and also promoted apoptosis in T-lymphocytes when treated with glucocorticoids [10]. Previous studies from our lab demonstrated a progressive expression of FTS with the progressive grades if cervical intraepithelial neoplasia (CIN) [11]. Disruption of FTS expression led to the shutdown of key elemental characteristics of the cervical cancer cells and resulted in apoptosis.…”