<p>α-E-Catenin (CTNNA1) Inhibits Cell Proliferation, Invasion and EMT of Bladder Cancer</p>

Abstract

Aim Bladder cancer (BLCA) is an urogenital system tumor with a high morbidity. We aimed to explore the function and potential mechanism of α-E-catenin (CTNNA1) in BLCA. Methods The CTNNA1 expression in BLCA tissues was detected using qRT-PCR and immunohistochemistry. QRT-PCR and Western blot were performed to measure the CTNNA1 expression in BLCA cell lines. CTNNA1 expression was up-regulated in T24 and UMUC-2 cells by CTNNA1 overexpression plasmid transfection. Cell proliferation, apoptosis, migration and invasion were respectively assessed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. The expression levels of epithelial–mesenchymal transition (EMT)-related factors were tested by qRT-PCR and Western blot. BLCA nude mice models were constructed to explore the effects of CTNNA1 on BLCA in vivo. Gene set enrichment analysis (GSEA) was proceeded to identify the CTNNA1-related pathways in BLCA. Results The expressions of CTNNA1 were down-regulated in BLCA tissues and cell lines, and its low expression indicated poor prognosis of BLCA patients. CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA cells. CTNNA1 enhanced E-cadherin expression and suppressed N-cadherin, snail, MMP2 and MMP9 expressions in BLCA cells, which suggested that CTNNA1 repressed EMT in BLCA cells. Moreover, CTNNA1 could inhibit tumor growth in vivo. CTNNA1 was positively associated with P53 and apoptosis pathways in BLCA cells. Conclusion CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA via activating P53 and apoptosis pathways. CTNNA1 might be a novel target in BLCA therapy.

Different impacts of TP53 mutations on cell cycle-related gene expression among cancer types

“…between patients with wild-type and mutant TP53 , and the lack of treatment data (treatment line, drugs, etc.). Instead, we found some reports that supported our findings of the prognosis, such as reports of poor prognosis for the TP53 mutation group in breast cancer 21 , 71 and bladder cancer 72 , and no prognostic impact of TP53 status in colon cancer and rectal cancer 24 , 73 . Moreover, we found some reports that supported our findings of the response to chemotherapy, such as reports of TP53 mutation as a marker of chemotherapy response in breast cancer 31 and bladder cancer 74 , and as a marker of resistance to chemotherapy in head and neck cancer 32 , 75 .…”

The Role of CTNNA1 in Malignancies: An Updated Review

“…Decreased expression of CTNNA1 and PTEN correlated with a high pathological stage of bladder cancer through immunohistochemical analysis of 133 cases of bladder cancer (P = 0.01) [72]. An analogous conclusion was reached using qRT-PCR and western blot analysis of bladder cancer tissues and cell lines [73]. Various pathways have been identified in bladder cancer exosomal proteins, including that of CTNNA1 [74].…”

“…Current reviews on the role of CTNNA1 in malignancies are limited mainly to HDGC [50,53,65,90,91]; however, this review covers the pathogenesis of multisystem solid tumors and leukemia. In addition, there are well-established methods for CTNNA1 detection, such as qRT-PCR [73], immunohistochemistry [58,73], exome sequencing [51], Sanger sequencing [64], and targeted nextgeneration sequencing [60]. While new techniques, including intravenous injection of apatite carbonate nanoparticles carrying relevant proteins [29] or ultrasound-guided intrauterine fluorescence-traceable lentiviral techniques carrying RNAi or Cre recombinase [84], can help to track CTNNA1.…”

Multiple programmed cell death patterns and immune landscapes in bladder cancer: Evidence based on machine learning and multi‐cohorts

“…63 Patients with BLCA having TP53 mutations have a poor prognosis and a higher pathological grade. 64 KMT2D is a recognized cancer-associated protein, in which mutations are associated with tumor size and death risk for patients. 65 In one study, longer survival and better prognosis was discovered for BLCA patients with KMT2D mutations, suggesting KMT2D as a potentially independent predictor of BLCA occurrence and prognosis.…”