TRIM59 induces epithelial‑to‑mesenchymal transition and promotes migration and invasion by PI3K/AKT signaling pathway in medulloblastoma

CD44 is a transmembrane glycoprotein, the phosphorylation of which can directly trigger intracellular signaling, particularly Akt protein, for supporting cell growth, motility and invasion. This study examined the role of CD44 on the progression of Cholangiocarcinoma (CCA) using metabolic profiling to investigate the molecular mechanisms involved in the Akt signaling pathway. Our results show that the silencing of CD44 decreases Akt and mTOR phosphorylation resulting in p21 and Bax accumulation and Bcl-2 suppression that reduces cell proliferation. Moreover, an inhibition of cell migration and invasion regulated by CD44. Similarly, the silencing of CD44 showed an alteration in the epithelial-mesenchymal transition (EMT), e.g. an upregulation of E-cadherin and a downregulation of vimentin, and the reduction of the matrix metalloproteinase (MMP)-9 signal. Interestingly, a depletion of CD44 leads to metabolic pathway changes resulting in redox status modification and Trolox (anti-oxidant) led to the recovery of the cancer cell functions. Based on our findings, the regulation of CCA progression and metastasis via the redox status-related Akt signaling pathway depends on the alteration of metabolic profiling synchronized by CD44.

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CEACAM6 promotes cholangiocarcinoma migration and invasion by inducing epithelial‑mesenchymal transition through inhibition of the SRC/PI3K/AKT signaling pathway

Oncology Letters ◽

10.3892/ol.2021.13157 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Chen Liu ◽

Min Wang ◽

Haitao Lv ◽

Bing Liu ◽

Xueqiang Ya ◽

...

Keyword(s):

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Mesenchymal Transition

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FERMT1 knockdown inhibits oral squamous cell carcinoma cell epithelial-mesenchymal transition by inactivating the PI3K/AKT signaling pathway

BMC Oral Health ◽

10.1186/s12903-021-01955-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiao Wang ◽

Qianqian Chen

Keyword(s):

Oral Cancer ◽

Signaling Pathway ◽

Cell Lines ◽

Western Blotting ◽

Epithelial Mesenchymal Transition ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Mesenchymal Transition ◽

Tgf Β1

Abstract Background The metastasis of oral cancer is one of the main causes of death. However, the mechanisms underlying oral cancer metastasis have not been completely elucidated. Fermitin family member 1 (FERMT1) plays an -oncogene role in many cancers; however, the role of FERMT1 in oral squamous cell cancer (OSCC) remains unclear. Methods In this study, OSCC cells were treated with 5 ng/ml recombinant human Transforming growth factor-β1 (TGF-β1) protein. FERMT1 expression was measured in OSCC cell lines by RT-qPCR and western blotting. The effect of FERMT1 knockdown on the migration and invasion of OSCC cells was evaluated by Transwell assay. The epithelial-mesenchymal transition (EMT) and PI3K/AKT signaling pathway-related mRNA expression and protein levels were assessed by RT-qPCR and western blotting. Results We found that FERMT1 expression was elevated in TGF-β1-induced OSCC cell lines, and knockdown of FERMT1 inhibited the migration and invasion in TGF-β1-induced OSCC cells. FERMT1 silencing inhibited vimentin, N-cadherin, matrix metalloproteinase 9 (MMP-9) expression and promoted E-cadherin expression, suggesting that FERMT1 silencing inhibited EMT in TGF-β1-induced OSCC cells. Furthermore, FERMT1 silencing inactivated the PI3K/AKT signaling pathway in TGF-β1-induced OSCC cells. Activation of the PI3K/AKT signaling pathway reversed the effect of FERMT1 silencing on OSCC cell migration, invasion, and EMT. Conclusions FERMT1 silencing inhibits the migration, invasion, and EMT of OSCC cells via inactivation of the PI3K/AKT signaling pathway, suggesting that FERMT1 is a novel and potential therapeutic target for anti-metastatic strategies for OSCC.

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TFAP4 Promotes Hepatocellular Carcinoma Invasion and Metastasis via Activating the PI3K/AKT Signaling Pathway

Disease Markers ◽

10.1155/2019/7129214 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Tao Huang ◽

Qi-Feng Chen ◽

Bo-Yang Chang ◽

Lu-Jun Shen ◽

Wang Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Disease Free Survival ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Invasion And Metastasis ◽

Term Survival ◽

Mesenchymal Transition ◽

Tumor Tissues

Transcription factor activating enhancer binding protein 4 (TFAP4) is established as a regulator of human cancer genesis and progression. Overexpression of TFAP4 indicates poor prognosis in various malignancies. The current study was performed to quantify TFAP4 expression as well as to further determine its potential prognostic value and functional role in patients with hepatocellular carcinoma (HCC). We identified that the expression of TFAP4 mRNA in 369 tumor tissues was higher than that in 160 normal liver tissues. Upregulated TFAP4 expressions were discovered in HCC cell lines compared to the healthy liver cell line, and similarly, the levels of TFAP4 were higher in tumor tissues than its expression in paratumor tissues. High mRNA and protein expression of TFAP4 was associated with worse overall survival (OS) and disease-free survival (DFS). Additionally, TFAP4 expression emerged as a risk factor independently affecting both OS and DFS of HCC patients. Functional studies demonstrated that TFAP4 increased HCC cell migration and invasion. Further investigations found that TFAP4 promotes invasion and metastasis by inducing epithelial-mesenchymal transition (EMT) and regulating MMP-9 expression via activating the PI3K/AKT signaling pathway in HCC. In conclusion, our study demonstrated that TFAP4 is a valuable prognostic biomarker in determining the likelihood of tumor metastasis and recurrence, as well as the long-term survival rates of HCC patients. Exploring the regulatory mechanism of TFAP4 will also contribute to the development of new prevention and treatment strategies for HCC.

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