ING5 inhibits lung cancer invasion and epithelial-mesenchymal transition by inhibiting the WNT/β-catenin pathway.

ING5 is the last member of the Inhibitor of Growth (ING) candidate tumor suppressor family that has been implicated in multiple cellular functions, including cell cycle regulation, apoptosis, and chromatin remodeling. Our previous study showed that ING5 overexpression inhibits lung cancer aggressiveness and epithelial-mesenchymal transition (EMT), with unknown mechanisms. Western blotting was used to detect total and phosphorylated levels of β-catenin and EMT-related proteins. Immunofluorescent staining was used to observe E-cadherin expression. Proliferation and colony formation, wound healing, and Transwell migration and invasion assays were performed to study the proliferative and invasive abilities of cancer cells. ING5 overexpression promotes phosphorylation of β-catenin at Ser33/37, leading to a decreased β-catenin protein level. Small hairpin RNA-mediated ING5 knockdown significantly increased the β-catenin level and inhibited phosphorylation of β-catenin S33/37. Treatment with the WNT/β-catenin inhibitor XAV939 inhibited ING5-knockdown promoted proliferation, colony formation, migration, and invasion of lung cancer A549 cells, with increased phosphorylation of β-catenin S33/37 and a decreased β-catenin level. XAV939 also impaired ING5-knockdown-induced EMT, as indicated by upregulated expression of the EMT marker E-cadherin, an epithelial marker; and decreased expression of N-cadherin, a mesenchymal marker, and EMT-related transcription factors, including Snail, Slug, Twist, and Smad3. Furthermore, XAV939 could inhibit the activation of both IL-6/STAT3 and PI3K/Akt signaling pathways. ING5 inhibits lung cancer invasion and EMT by inhibiting the WNT/β-catenin pathway.

Liu XL ，Meng J ，Zhang XT ，Liang XH ，Zhang F ，Zhao GR ，Zhang T ... -  《-》

ING5 knockdown enhances migration and invasion of lung cancer cells by inducing EMT via EGFR/PI3K/Akt and IL-6/STAT3 signaling pathways.

Liu XL ，Zhang XT ，Meng J ，Zhang HF ，Zhao Y ，Li C ，Sun Y ，Mei QB ，Zhang F ，Zhang T ... -  《Oncotarget》

ING5 inhibits cancer aggressiveness via preventing EMT and is a potential prognostic biomarker for lung cancer.

Zhang F ，Zhang X ，Meng J ，Zhao Y ，Liu X ，Liu Y ，Wang Y ，Li Y ，Sun Y ，Wang Z ，Mei Q ，Zhang T ... -  《Oncotarget》

WSTF promotes proliferation and invasion of lung cancer cells by inducing EMT via PI3K/Akt and IL-6/STAT3 signaling pathways.

Williams syndrome transcription factor (WSTF), which is encoded by the BAZ1B gene, was first identified as a hemizygously deleted gene in patients with Williams syndrome. WSTF protein has been reported to be involved in transcription, replication, chromatin remodeling and DNA damage response, and also functions as a tyrosine protein kinase. However, the function of WSTF in cancer is not known. Here, we show that WSTF overexpression promotes proliferation, colony formation, migration and invasion of lung cancer A549 and H1299 cells. WSTF overexpression also promotes tumor growth and invasive abilities of lung cancer cells in mouse xenograft models. cDNA microarray and subsequent qRT-PCR validation revealed that WSTF overexpression significantly upregulated the expression of EMT (epithelial to mesenchymal transition) marker fibronectin (FN1) and EMT-inducing genes Fos and CEACAM6. The changes of EMT markers including downregulated E-cadherin and upregulated N-cadherin and FN1 were further confirmed at both mRNA and protein levels upon WSTF overexpression, with typical morphological changes of EMT. Furthermore, WSTF activates both PI3K/Akt and IL-6/STAT3 oncogenic signaling pathways. Treatment with PI3K inhibitor ZSTK474 or STAT3 inhibitor niclosamide reversed the effects of WSTF overexpression by inhibiting cell proliferation, migration and invasion, with decreased level of p-Akt, p-STAT3 and IL-6. ZSTK474 and niclosamide also reversed EMT markers and EMT-inducing proteins including Snail, Slug, Twist and CEACAM6 in WSTF-overexpressing A549 cells. Taken together, these results demonstrate that WSTF may act as an oncoprotein in lung cancer to accelerate tumor aggressiveness by promoting EMT via activation of PI3K/Akt and IL-6/STAT3 pathways.

Meng J ，Zhang XT ，Liu XL ，Fan L ，Li C ，Sun Y ，Liang XH ，Wang JB ，Mei QB ，Zhang F ，Zhang T ... -  《-》

CBX8 Promotes Epithelial-mesenchymal Transition, Migration, and Invasion of Lung Cancer through Wnt/β-catenin Signaling Pathway.

Lung cancer (LC) is primarily responsible for cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features and is associated with the development of tumors. CBX8, a member of the PcG protein family, plays a critical role in various cancers, containing LC. However, specific regulatory mechanisms of CBX8 in LC progression are not fully understood. This study aimed to investigate the regulatory role of CBX8 in LC progression. Bioinformatics was used to analyze the relationship between CBX8 level and tumor and the enrichment pathway of CBX8 enrichment. qRT-PCR was used to detect the differential expression of CBX8 in LC cells and normal lung epithelial cells. The effects of knockdown or overexpression of CBX8 on the proliferation, migration and invasion of LC cells were evaluated by CCK- -8 assay and Transwell assay, and the levels of proteins associated with the EMT pathway and Wnt/ β-catenin signaling pathway were detected by western blot. Bioinformatics analysis revealed that CBX8 was highly expressed in LC and enriched on the Wnt/β-catenin signaling pathway. The expression level of CBX8 was significantly elevated in LC cells. Knockdown of CBX8 significantly inhibited cell proliferation, migration and invasion, and decreased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. Conversely, overexpression of CBX8 promoted cell proliferation, migration and invasion, and increased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. The Wnt inhibitor IWP-4 alleviated the effects produced by overexpression of CBX8. Collectively, these data demonstrated that CBX8 induced EMT through Wnt/β-- catenin signaling, driving migration and invasion of LC cells.

Cai X ，Lv Y ，Pan J ，Cao Z ，Zhang J ，Li Y ，Zheng H ... -  《-》