TUSC3 promotes colorectal cancer progression and epithelial-mesenchymal transition (EMT) through WNT/β-catenin and MAPK signalling

Abstract

Colorectal cancer (CRC) is one of the most common malignancies and is the second leading cause of cancer death in humans. Tumour suppressor candidate 3 (TUSC3) plays an important role in embryogenesis and metabolism. Deletion of TUSC3 often causes non-syndromic mental retardation. Even though TUSC3 deregulation is frequently observed in epithelial cancers, the function of TUSC3 in CRC has remained unknown. In this study, we observed greater expression of TUSC3 at the mRNA and protein level in clinical colorectal tumour samples compared with paired normal tissues. Gain- and loss-of-function analyses were performed to evaluate the functional significance of TUSC3 in CRC initiation and progression. Immunoblotting, immunofluorescence, and co-immunoprecipitation analyses were used to identify potential pathways with which TUSC3 might be involved. Overexpression of TUSC3 in CRC cells induced epithelial-mesenchymal transition (EMT) in CRC cells, accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation, migration, and invasion, as well as accelerated xenograft tumour growth, were observed in TUSC3-overexpressing CRC cells, while opposite effects were achieved in TUSC3-silenced cells. In conclusion, our study demonstrated the oncogenic role of TUSC3 in CRC and showed that TUSC3 may be responsible for alternations in the proliferation ability, aggressiveness, and invasive/metastatic potential of CRC through regulating the MAPK, PI3K/Akt, and Wnt/β-catenin signalling pathways.

Annexin A3 depletion overcomes resistance to oxaliplatin in colorectal cancer via the MAPK signaling pathway

“…Inhibition of the MAPK signaling pathway blocks cell invasion in lung cancer . It also participates in CRC progression and epithelial‐to‐mesenchymal transition . Blocking this pathway thus may help treat CRC .…”

AF1q Mediates Tumor Progression in Colorectal Cancer by Regulating AKT Signaling

“…Colorectal cancer (CRC) is the third most common human malignant neoplasm worldwide, and prognosis varies significantly between early- and late-stage diseases [1,2]. The five-year overall survival (OS) rate of stage II CRC patients is as high as 80% following surgery, but this drops to 40–60% for stage III CRC patients, who display evidence of tumor invasion and regional lymph node metastasis [3].…”

Decreased carbonyl reductase 1 expression promotes tumor growth via epithelial mesenchymal transition in uterine cervical squamous cell carcinomas

“…It is unclear how CBR1 regulates EMT. In this study, it was found that CBR1 suppression stimulated the intracellular signaling pathways of TGF‐β and Wnt/β‐catenin (Table ), both of which have been reported to play roles in regulating EMT . The authors speculate that CBR1 regulates EMT by interacting with the TGF‐β and Wnt/β‐catenin pathways.…”