FAM107A Inactivation Associated with Promoter Methylation Affects Prostate Cancer Progression through the FAK/PI3K/AKT Pathway

Ke, Shuai; Liu, Zelin; Wang, Qinghua; Zhai, Guanzhong; Shao, Haoren; Yu, Xi; Guo, Jia

doi:10.3390/cancers14163915

Cited by 12 publications

(9 citation statements)

References 38 publications

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“…The FAK/PI3K/AKT signaling pathway is a pivotal player in cell proliferation, metastasis, and survival processes (Guo et al 2020 ; Ke et al 2022 ; Chen et al 2023 ; Ye et al 2023 ). Our findings indicate that flavokawain C is capable of downregulating the FAK/PI3K/AKT signaling pathway through the inhibition of FAK and PI3K phosphorylation (Fig.…”

Section: Discussionmentioning

confidence: 99%

Flavokawain C inhibits proliferation and migration of liver cancer cells through FAK/PI3K/AKT signaling pathway

Wang,

Li,

Yang

et al. 2024

J Cancer Res Clin Oncol

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Purpose This study investigated the potential applicability and the underlying mechanisms of flavokawain C, a natural compound derived from kava extracts, in liver cancer treatment. Methods Drug distribution experiment used to demonstrate the preferential tissues enrichment of flavokawain C. Cell proliferation, apoptosis and migration effect of flavokawain C were determined by MTT, colony formation, EdU staining, cell adhesion, transwell, flow cytometry and western blot assay. The mechanism was explored by comet assay, immunofluorescence assay, RNA-seq-based Kyoto encyclopedia of genes and genomes analysis, molecular dynamics, bioinformatics analysis and western blot assay. The anticancer effect of flavokawain C was further confirmed by xenograft tumor model. Results The studies first demonstrated the preferential enrichment of flavokawain C within liver tissues in vivo. The findings demonstrated that flavokawain C significantly inhibited proliferation and migration of liver cancer cells, induced cellular apoptosis, and triggered intense DNA damage along with strong DNA damage response. The findings from RNA-seq-based KEGG analysis, molecular dynamics, bioinformatics analysis, and western blot assay mechanistically indicated that treatment with flavokawain C notably suppressed the FAK/PI3K/AKT signaling pathway in liver cancer cells. This effect was attributed to the induction of gene changes and the binding of flavokawain C to the ATP sites of FAK and PI3K, resulting in the inhibition of their phosphorylation. Additionally, flavokawain C also displayed the strong capacity to inhibit Huh-7-derived xenograft tumor growth in mice with minimal adverse effects. Conclusions These findings identified that flavokawain C is a promising anticancer agent for liver cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Flavokawain C inhibits proliferation and migration of liver cancer cells through FAK/PI3K/AKT signaling pathway

Wang,

Li,

Yang

et al. 2024

J Cancer Res Clin Oncol

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“…The results suggested that YEATS2 was related to the PI3K/AKT signaling pathway and extracellular matrix (ECM). Activation of the PI3K/AKT pathway is associated with the malignancy of a variety of tumors, including gastric cancer, leukemia, prostate cancer, and breast cancer [ 27 , 28 , 29 , 30 ]. PI3K/AKT and downstream molecule mTOR can promote tumor proliferation, survival, metastasis, and invasion, and inhibit autophagy and senescence [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of YEATS2 Remodels the Extracellular Matrix to Promote Hepatocellular Carcinoma Progression via the PI3K/AKT Pathway

Liu

Hu²,

et al. 2023

Cancers

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Hepatocellular carcinoma (HCC) is one of the most common cancers and the fourth leading cause of death in men. YEATS domain containing 2 (YEATS2) gene encodes a scaffolding subunit of the ATAC complex. We found that YEATS2 was upregulated in HCC tissues and was associated with a poor prognosis. However, the role of YEATS2 in HCC remains unclear. The purpose of this study was to investigate the effect of YEATS2 on the progression of HCC and to elucidate its related mechanisms. We found that overexpression of YEATS2 promoted tumor cell proliferation, migration, and invasion through the PI3K/AKT signaling pathway and regulation of extracellular matrix. These findings help to understand the role of YEATS2 in HCC, and YEATS2 may become a new target for HCC therapy.

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“…In the cytoplasm, activated FAK initiates survival pathways in a PI3K and MAPK-dependent manner. Simultaneously, within the nucleus, the FERM domain of FAK hinders the activation of p53, thereby preventing inherent cell apoptosis ( Del et al, 2022 ; Ke et al, 2022 ). Previous studies have delineated various mechanisms through which FAK promotes tumor cell survival and proliferation.…”

Section: Role Of Fak In the Occurrence And Development Of Tumorsmentioning

confidence: 99%

Roles and inhibitors of FAK in cancer: current advances and future directions

Hu,

Wang,

Shang

et al. 2024

Front. Pharmacol.

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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK’s role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies.

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FAM107A Inactivation Associated with Promoter Methylation Affects Prostate Cancer Progression through the FAK/PI3K/AKT Pathway

Cited by 12 publications

References 38 publications

Flavokawain C inhibits proliferation and migration of liver cancer cells through FAK/PI3K/AKT signaling pathway

Flavokawain C inhibits proliferation and migration of liver cancer cells through FAK/PI3K/AKT signaling pathway

Overexpression of YEATS2 Remodels the Extracellular Matrix to Promote Hepatocellular Carcinoma Progression via the PI3K/AKT Pathway

Roles and inhibitors of FAK in cancer: current advances and future directions

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