ZNF703 Overexpression may act as an oncogene in non‐small cell lung cancer

Abstract

Despite therapeutic advances, lung cancer remains one of the most common causes of cancer‐related deaths worldwide. The ZNF703 gene has been identified as the driver of the 8p11‐12 region and its amplification or overexpression has been associated with several types of cancers. It has also been shown that ZNF703 overexpression can activate the Akt/mTOR signaling pathway. The aim of our study was to investigate the role of the ZNF703 gene in association with Akt/mTOR activation in non‐small cell lung cancer (NSCLC). Expression levels in tumors and matched noncancerous tissue samples from 47 patients were analyzed by qRT‐PCR and the Akt phosphorylation levels were investigated by Western blotting. Our results show that ZNF703 is up‐regulated in 63.4% of NSCLC tumor samples. Althogh the correlation did not reach a statistically significant level Akt phosphorylation was increased in tumor tissues expressing high levels of ZNF703. The role of the ZNF703 gene has not been investigated in NSCLC. Our data show that ZNF703 may contribute to tumor development in NSCLC by activating the Akt/mTOR pathway.

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

“…In this study , we found that the loss of ZNF703 expression decreased the expression of p-PI3K, p-Akt, and p-GSK-3β. These results are similar to the findings of the study by Baykara et al in which ZNF703 was shown to contribute to tumour development in NSCLC by activating the Akt/mTOR pathway [12]. To specifically determine the effects of PI3K and Akt on the ZNF703-mediated promotion of cell proliferation and metastasis, we father employed the Akt inhibitor MK2206 and the PI3K inhibitor LY294002 to inhibit the expression of Akt and PI3K, respectively, in ZNF703-upregulated cells.…”

“…The overexpression of ZNF703 is thought to play an important role in various human cancers [12, 13, 15, 23]; however, the role and molecular mechanism if ZNF703 are not well understood in OSCC.…”

“…Members of the NET (for NocA, Nlz, Elbow, and TLP-1) family have recently been shown to play important roles in embryonic development and tumour progression [9, 10]. It has been shown that ZNF703 is overexpressed in several types of malignancies, including breast cancer [11], lung cancer [12], gastric cancer [13], colorectal cancer [14] and cholangiocarcinoma [15], and its high expression promotes the progression of these cancers. Investigations have confirmed that ZNF703 can complex with Groucho and repress E-cadherin, Wnt and TGF-β reporter expression to regulate cell adhesion, migration, and proliferation in breast cancer [16].…”

“…Overexpressed ZNF703 was shown to increase lung metastases in a mouse model of breast cancer and to be an independent unfavourable prognostic factor for the survival of patients with luminal B breast cancer [11, 17]. In addition, overexpressed ZNF703 was shown to contribute to tumour progression in non-small cell lung cancer by activating the Akt/mTOR signalling pathway [12]. However, the role and molecular mechanism of ZNF703 in OSCC are still unclear.…”

Increased expression of ZNF 703 in breast cancer tissue: An opportunity for RNAi–NSAID combinatorial therapy

“…Baykara et al. data also show that ZNF703 may contribute to tumor development in NSCLC by activating the Akt/mTOR pathway. Additionally, Ma et al.…”