Downregulation of IQGAP1 inhibits epithelial‐mesenchymal transition via the HIF1α/VEGF‐A signaling pathway in gastric cancer. Issue 9 (15th May 2019)

• Record Type: Journal Article
• Authors: Liu, Junqiang; Ni, Xiufan; Li, Yafang; Chen, Mengjiao; Chen, Wei; Wu, Ying; Chen, Baoding; Wu, Yan; Xu, Min
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 9(2019)
• Page Start: 15790
• Page End: 15799
• Publication Date: 2019-05-15
• Subjects: EMT -- gastric cancer -- HIF1α -- IQGAP1 -- VEGF‐A; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28849
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: As an oncogene, IQ‐domain GTPase‐activating protein 1 (IQGAP1) regulates the epithelial‐mesenchymal transition (EMT) of several cancers, such as breast cancer, thyroid cancer, and esophageal squamous cell carcinoma. However, the role of the scaffold protein IQGAP1 on EMT in gastric cancer remains unclear. Therefore, the present work was performed to address the question. Our results showed that IQGAP1 expression is upregulated in human gastric cancer specimens and cell lines. Furthermore, IQGAP1 knockdown inhibited the migratory ability of gastric cancer cells and reduced the expression of mesenchymal phenotype markers, including Slug, β‐catenin, Snail, Vimentin, and N‐cadherin, as well as vascular endothelial growth factor‐A (VEGF‐A) secretion in gastric cancer cells. Conversely, IQGAP1 downregulation increased the epithelial phenotype marker E‐cadherin. Furthermore, IQGAP1 silencing not only downregulated hypoxia‐inducible transcription factor 1α (HIF1α) but also limited its translocation from the cytosol to the nucleus. Collectively, our results indicated that EMT was regulated by IQGAP1, which was associated with VEGF‐A, since other data demonstrated that HIF1α was involved in VEGF‐A expression. Therefore, we speculated that IQGAP1 regulated EMT of gastric cancer partially via the HIF1α/VEGF‐A signaling pathway. IQGAP1 may serve as an effective therapeutic biomarker for gastric cancer. Abstract : Downregulation of IQGAP1 inhibits epithelial‐mesenchymal transition (EMT) of gastric cancer cells via suppressing the translocation of hypoxia‐inducible transcription factor 1α (HIF1α) to nuclear and vascular endothelial growth factor‐A (VEGF‐A) expression and secretion. Our study also suggested that the knockdown of IQGAP1 may be a potential therapeutic strategy and may provide a theoretical basis for therapeutic targets for gastric cancer.