Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma

Li, Guoyin; Song, Zewen; Wu, Changjing; Li, Xiaoyan; Zhao, Liping; Tong, Binghua; Guo, Zhenni; Sun, Meiqing; Zhang, Huina; Jia, Lintao; Li, Shengqing; Wang, Lei

doi:10.1186/s12967-022-03247-4

Cited by 14 publications

(10 citation statements)

References 41 publications

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“…In lung cancer, FBXW2 can inhibit the proliferation and metastasis of lung cancer by activating EGFR signaling pathway [43]. EGFR signaling can promote the proliferation of lung adenocarcinoma by downregulating the E3 ligase NEDD4L [44]. Studies have shown that AKT signaling can be activated by EGFR signaling in a variety of ways [45,46].…”

Section: Discussionmentioning

confidence: 99%

PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer

Kong,

jiang,

Zhou

et al. 2023

Preprint

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Background: Lung cancer stands as the second most prevalent malignant neoplasm worldwide. Addressing the underlying mechanisms propelling the progression of non-small cell lung cancer is of paramount importance. In this study, we have elucidated the pivotal role of PHF12 in this context. Materials and Methods: We harnessed clinical lung cancer tissue samples and non-small cell lung cancer cell lines to discern the expression pattern of PHF12. In vitro assays probing cell proliferation were conducted to substantiate the functional impact of PHF12. Furthermore, an in vivo Xenograft model was employed to dissect the role of PHF12. Employing ChIP assays and qRT-PCR, we delved into the intricate binding dynamics between PHF12 and HDAC1. Mechanistic insights into the PHF12-HDAC1 axis in lung cancer progression were pursued via RNA-seq and GSEA analyses. Results Notably, PHF12 exhibited a substantial upregulation within tumor tissue, concomitant with its correlation to HDAC1. The trilogy of cell proliferation assays, transwell assays, and the Xenograft model collectively underscored the promoting influence of PHF12 on lung cancer proliferation, both in vitro and in vivo. The ChIP assay unveiled the transcriptional regulatory role of PHF12 in governing HDAC1 expression. This correlation extended to both mRNA and protein levels. Intriguingly, the rescue of function within NSCLC cell lines post PHF12 knockdown was achievable through HDAC1 overexpression. Additionally, our findings unveiled the capacity of the PHF12-HDAC1 axis to activate the EGFR/AKT signaling pathway, thereby further corroborating its significance in lung cancer progression. Conclusion Our study identified PHF12 as an oncogenic role in lung cancer proliferation for the first time. PHF12 transcriptionally regulate HDAC1 and activate EGFR/AKT signaling pathway in NSCLC progression. PHF12 may serve as an important target in lung cancer therapy.

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Section: Discussionmentioning

confidence: 99%

PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer

Kong,

jiang,

Zhou

et al. 2023

Preprint

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“…The immunohistochemical and immunofluorescence analysis of the FFPE sections were performed as previously described. [ 22 ] The Ki67 (ab16667, Abcam) antibody was used for immunostaining, while the BCL2, BAX, phospho‐EGFR, phospho‐PI3K, phospho‐AKT, and phospho‐SRC antibodies were used to achieve immunofluorescence. Imaging was performed using confocal laser scanning microscopy.…”

Section: Methodsmentioning

confidence: 99%

“…The CCK‐8 assay was performed as previously described. [ 22 ] The 5637 cells were treated with different concentrations of TPL, HSP, and THE NPs for 48 h (concentrations = 0, 2, 10, 50, 250, 500, 1000, 2000, and 4000 nM). n = 4.…”

Section: Methodsmentioning

confidence: 99%

Small‐molecule nanoprodrug with high drug loading and EGFR, PI3K/AKT dual‐inhibiting properties for bladder cancer treatment

Song

et al. 2023

Exploration

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Bladder cancer (BCa) is one of the most common malignancies worldwide. Although multiple efforts have been made, the 5‐year survival rate of patients with BCa remains unchanged in recent years. Overexpression of the epidermal growth factor receptor (EGFR) is found in ≈74% of BCa tissue specimens; however, current EGFR‐based targeted therapies show little benefit for BCa patients, as the EGFR downstream pathways appear to be circumvented by other receptor tyrosine kinases (RTKs). In this study, two natural products are identified, namely triptolide (TPL) and hesperidin (HSP), that target and inhibit the EGFR and its downstream PI3K/AKT pathway in BCa. To synergistically combine triptolide and hesperidin, a succinic acid linker was employed to conjugate them and formed an amphiphilic TPL‐HSP EGFR‐targeting prodrug (THE), which further self‐assembled to generate nanoparticles (THE NPs). These NPs allowed the EGFR‐targeted delivery of the triptolide and hesperidin, and simultaneous inhibition of the EGFR and PI3K/AKT both in vitro and in vivo. This study provides a promising EGFR‐targeted delivery approach with the dual inhibition of the EGFR and PI3K/AKT, while also exhibiting a high drug loading and low toxicity. Our formulation may be a suitable option to deliver natural products for BCa treatment by EGFR‐targeted therapy.

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“…The HCC samples and corresponding tumor adjacent normal tissues were fabricated into a tissue chip. IHC staining of FFPE sections was performed as described in our previous studies [ 41 , 42 ]. IHC samples were scored by two independent pathologists, according to criteria used in previous published studies [ 43 , 44 ].…”

Section: Methodsmentioning

confidence: 99%

Copper metabolism-related risk score identifies hepatocellular carcinoma subtypes and SLC27A5 as a potential regulator of cuproptosis

Li,

Wang,

Guo

et al. 2023

Aging

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Aims: Dysregulated copper metabolism has been noticed in many types of cancer including hepatocellular carcinoma (HCC); however, a comprehensive understanding about this dysregulation still remains unclear in HCC. Methods: A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of copper metabolism-related genes. A related risk score, termed as CMscore, was developed via univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression. Pathway enrichment analyses and tumor immune cell infiltration were further investigated in CMscore stratified HCC patients. Weighted correlation network analysis (WGCNA) was used to identify potential regulator of cuproptosis. Results: Copper metabolism was dysregulated in HCC. HCC patients in the high-CMscore group showed a significantly lower overall survival (OS) and enriched in most cancer-related pathways. Besides, HCC patients with high CMscore had higher expression of pro-tumor immune infiltrates and immune checkpoints. Moreover, cancer patients with high CMscore from two large cohorts exhibited significantly prolonged survival time after immunotherapy. WGCNA and subsequently correlation analysis revealed that SLC27A5 might be a potential regulator of cuproptosis in HCC. In vitro experiments revealed that SLC27A5 inhibited cell proliferation and migration of HCC cells and could upregulate FDX1, the key regulator of cuproptosis. Significance: The CMscore is helpful in clustering HCC patients with distinct prognosis, gene mutation signatures, and sensitivity to immunotherapy. SLC27A5 might serve as a potential target in the induction of cuproptosis in HCC.

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Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma

Cited by 14 publications

References 41 publications

PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer

PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer

Small‐molecule nanoprodrug with high drug loading and EGFR, PI3K/AKT dual‐inhibiting properties for bladder cancer treatment

Copper metabolism-related risk score identifies hepatocellular carcinoma subtypes and SLC27A5 as a potential regulator of cuproptosis

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