TBLR1 is a novel prognostic marker and promotes epithelial–mesenchymal transition in cervical cancer

Abstract

Background:Invasion and metastasis remain a critical issue in cervical cancer. However, the underlying mechanism of it in cervical cancer remains unclear. The newly discovered protein, TBLR1, plays a crucial role in regulating various key cellular functions.Methods:In this study, western blot, real-time RT–PCR, immunohistochemical staining, 3D morphogenesis Matrigel culture, wound healing and Boyden chamber invasion assays, xenografted tumour model, luciferase assays, and chromatin immunoprecipitation assays were used.Results:The expression of TBLR1 in cervical cancer cell lines and tissues was significantly upregulated at both the RNA and protein levels compared with that in normal cervical cells. Statistical analysis suggested that TBLR1 as an independent prognostic factor was significantly correlated with the clinical stage, survival time and recurrence. Moreover, overexpression of TBLR1 in Hela and Siha cell lines promoted invasion in vitro and in vivo with the increases of the mesenchymal factors vimentin and fibronectin and decreases of the epithelial marker α-catenin. In contrast, RNAi-mediated knockdown of TBLR1 inhibited epithelial–mesenchymal transition in vitro and in vivo. Further study indicated that this might be mediated via the NF-κB and Wnt/β-Catenin signalling pathway, and involve regulation of Snail and Twist.Conclusions:The TBLR1 protein may be a prognostic marker in cervical cancer and play an important role in the invasion and metastasis of human cervical cancer.

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

“…It reduces the expression of β-catenin (epithelial marker) and increases the expression of Vim1 and fibronectin (mesenchymal markers). It increases the invasive properties of cervical cancer cells and further activates the NF-kB and Wnt/bcatenin pathways to regulate the expressions of SNAI1 and Twist in cervical cancer [88].…”

“…TBLR1 plays a role in the induction of EMT and is associated with pelvic lymph node metastasis and prognosis in stage Ia2-IIa2 in cervical cancer patients. TBLR1 is of great clinical value as a potential early biomarker to improve the diagnosis and prognostic assessment of cervical cancer patients [88]. Sam68 causes lymph node metastasis in cervical cancer patients by inducing EMT.…”

“…Sam68 causes lymph node metastasis in cervical cancer patients by inducing EMT. It acts as an independent prognostic factor for predicting overall survival and disease-free survival in patients with early-stage cervical cancer [88]. EphB2 could act as a diagnostic marker of EMT [58].…”

Cytoplasmic, full length and novel cleaved variant, TBLR1 reduces apoptosis in prostate cancer under androgen deprivation

“…TBLR1 is overexpressed in several types of cancer and functions as an oncogene by activation of important intracellular signaling pathways including the Wnt-β-catenin pathway and the nuclear factor-kappa (NF-kB) pathway [11, 24]. TBLR1 expression has a positive correlation with disease progression, tumor metastasis, and drug resistance [16–18, 25–27]. Our previous study has shown that TBLR1 is a transcriptional activator of AR and its nuclear expression is significantly reduced in PCa compared with benign prostate glands.…”

“…TBLR1 is also a strong coactivator of AR in prostate cancer, leading to selective activation of growth suppressive AR target genes and tumor suppression. In contrast to the reduced expression of TBLR1 in PCa, expression of TBLR1 is upregulated in breast, colon, esophageal squamous cell and nasopharyngeal carcinomas (NPC) and is a potential prognostic marker for aggressive cervical cancer [16–18]. Overexpression of TBLR1in NPC cells causes reduced sensitivity to cisplatin-induced apoptosis [18].…”