Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma

AbstractAberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/β-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of β-catenin and inhibited Wnt/β-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/β-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target.

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FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer

Open Medicine ◽

10.1515/med-2021-0232 ◽

2021 ◽

Vol 16 (1) ◽

pp. 419-427

Author(s):

Wenfeng He ◽

Xia Liu ◽

Zhijie Luo ◽

Longmei Li ◽

Xisheng Fang

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Untranslated Region ◽

Target Gene ◽

Regulatory Mechanism ◽

The Novel ◽

Accelerated Growth ◽

High Level ◽

Cancer Tissues ◽

Great Damage

Abstract FGF16 is implicated in the progression of some specific types of cancers, such as embryonic carcinoma, ovarian cancer, and liver cancer. Yet, the function of FGF16 in the development of lung cancer remains largely unexplored. In this study, we present the novel function of FGF16 and the regulation of miR-520b on FGF16 in lung cancer progression. In clinical lung cancer tissues, FGF16 is overexpressed and its high level is negatively associated with the low level of miR-520b. Furthermore, both the transcription and translation levels of FGF16 are restrained by miR-520b in lung cancer cells. For the regulatory mechanism investigation, miR-520b is able to directly bind to the 3′-untranslated region (3′UTR) of FGF16 mRNA, leading to its mRNA cleavage in the cells. Functionally, miR-520b reduces the growth of lung cancer and its inhibitor anti-miR520b is able to promote the growth through competing endogenous miR-520b. Moreover, FGF16 silence using RNA interference is capable of doing great damage to anti-miR-520b-accelerated growth of lung cancer. Thus, our finding indicates that FGF16 is a new target gene of miR-520b in lung cancer. For lung cancer, FGF16 may serve as a novel biomarker and miR-520b/FGF16 may be useful in clinical treatment.

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Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis

British Journal of Cancer ◽

10.1038/sj.bjc.6601205 ◽

2003 ◽

Vol 89 (5) ◽

pp. 877-885 ◽

Cited By ~ 205

Author(s):

M I Koukourakis ◽

◽

A Giatromanolaki ◽

E Sivridis ◽

G Bougioukas ◽

...

Keyword(s):

Lung Cancer ◽

Lactate Dehydrogenase ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Small Cell ◽

Angiogenic Factor ◽

Tumour Hypoxia ◽

Small Cell Lung ◽

Cancer Tissues

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MiR-129-5p inhibits liver cancer growth by targeting calcium calmodulin-dependent protein kinase IV (CAMK4)

Cell Death and Disease ◽

10.1038/s41419-019-1923-4 ◽

2019 ◽

Vol 10 (11) ◽

Cited By ~ 7

Author(s):

Zhengzhao Li ◽

Junyu Lu ◽

Guang Zeng ◽

Jielong Pang ◽

Xiaowen Zheng ◽

...

Keyword(s):

Protein Kinase ◽

Liver Cancer ◽

Target Gene ◽

Liver Cells ◽

Migration And Invasion ◽

Dependent Protein Kinase ◽

Calcium Calmodulin Dependent ◽

Dependent Protein ◽

Direct Target ◽

Cancer Tissues

Abstract This study was designed to investigate the mechanism by which miR-129-5p affects the biological function of liver cancer cells. The expression levels of miR-129–5p in liver cancer tissues and cells were, respectively, determined. Crystal violet staining and flow cytometry were used to detect cell proliferation and apoptosis. Wound healing assay and transwell assay were performed to test cell migration and invasion. The target gene of miR-129–5p was analyzed and verified by bioinformatics analysis and luciferase reporter assay. Tumorigenicity assays in nude mice were used to test the antitumor ability of calcium calmodulin-dependent protein kinase IV (CAMK4). miR-129–5p was found to be underexpressed in hepatocellular cancer tissues and cells and also to inhibit liver cells proliferation, migration, and invasion and promote apoptosis. CAMK4 was a direct target for miR-129–5p and was lowly expressed in liver cancer tissues and cells. CAMK4 was also found to inhibit liver cells proliferation, migration and invasion, and promote apoptosis. CAMK4 might exert an antitumor effect by inhibiting the activation of mitogen-activated protein kinase (MAPK). MiR-129–5p was a tumor suppressor with low expression in liver cancer tissues and cells. CAMK4, which is a direct target gene of miR-129–5p, could inhibit tumor by inhibiting the activation of MAPK signaling pathway.

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YAP mediates the positive regulation of hnRNPK on the lung adenocarcinoma H1299 cell growth

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz053 ◽

2019 ◽

Vol 51 (7) ◽

pp. 677-687

Author(s):

Lipei Xu ◽

Tingting Zhang ◽

Wensi Huang ◽

Xiaohui Liu ◽

Junlei Lu ◽

...

Keyword(s):

Lung Cancer ◽

Cell Growth ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Contact Inhibition ◽

Negative Regulator ◽

Cell Contact ◽

Reporter System ◽

H1299 Cell ◽

Multifunctional Protein

AbstractLung cancer is the leading cause of cancer death worldwide, and non-small cell lung cancer (NSCLC) accounts for 80%–85% of diagnostic cases. The molecular mechanisms of NSCLC pathogenesis are not well understood. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional protein that regulates gene expression and signal transduction and closely associated with tumorigenesis, but its mechanism of action in the pathogenesis of NSCLC is unclear. In this study, we observed that the expression pattern of hnRNPK in H1299 lung adenocarcinoma cells varied depending on the cell density in culture. Moreover, hnRNPK stimulated the ability of proliferation and colony formation of H1299 cells, which is important for the multilayered cell growth in culture. We further investigated whether there is an association between hnRNPK and the elements involved in the cell contact inhibition pathway. By using quantitative reverse transcriptase-polymerase chain reaction assay and a YAP activity reporter system, we found that hnRNPK upregulated the mRNA and protein levels and transcriptional activity of Yes-associated protein 1 (YAP), a master negative regulator of Hippo contact inhibition pathway. Furthermore, YAP knockdown with siRNA abolished the stimulatory effect of hnRNPK on H1299 cell proliferation. These results suggested that YAP could be one of the effectors of hnRNPK. Our data may provide new clues for further understanding the biological functions of hnRNPK, particularly in the context of lung adenocarcinoma oncogenesis.

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Epitope mapping of epidermal growth factor receptor (EGFR) in lung cancer using immunohistochemistry: Fine tuning the protocols

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21162 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21162-21162

Author(s):

J. TIMAR ◽

K. Derecskei ◽

B. Dome ◽

J. Moldvay

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Ligand Binding ◽

Lung Adenocarcinoma ◽

Growth Factor Receptor ◽

Fine Tuning ◽

Antigen Retrieval ◽

Egfr Expression ◽

Lung Adenocarcinomas ◽

Cancer Tissues

21162 Background: Until now, immunohistochemistry was not able to become a reliable diagnostic approach for EGFR targeted therapies. The golden standard of the determination of EGFR protein expression in paraffin embedded cancer tissues is the EGFRpharmDXtm kit. Methods: Here we show data based on analysis of 110 lung adenocarcinomas, that the recommended protocol may not be optimal for ideal performance of the immunodetection, since microwave retrieval, extended primary antibody-incubation time and replacement of the developer reagent converted four EGFR-negative tumor into EGFR protein positive out of eight lung adenocarcinoma cases. Protocol modification improved the performance of another widely used EGFR-kit, Ventana's CONFIRM, where replacement of the protease antigen retrieval with microwave cooking converted several EGFR-negative tumors to strongly positive. Meanwhile both EGFR-kits detect EGFR expression (juxtamembrane domain) but do not provide information on the expression of epitopes critical from the point of view of targeted therapy. Results: We have developed two protocols, which can detect the ligand-binding (AB-10, BioMarkers) and C-terminal (AB- 335, Biogenex) cytoplasmic domains of the EGFR protein in paraffin embedded lung cancer tissues. We have shown, based on the analysis of more than 110 lung adenocarcinoma tissues, that the ligand binding domain of EGFR is rarely expressed while the C-terminal domain is ubiquitously expressed in EGFR-PharmDX and CONFIRM-positive cancers. The biological activity of EGFR can be characterized either by autophosphorylation of the receptor or by detection of divers phosphorylated downstream signaling components. We have found that unlike p1086 (detected by a Zymed antibody), the p1173 site of EGFR (identified by a rabbit monoclonal of Epitomics) can be detected 27/110 paraffin embedded lung adenocarcinomas. Conclusions: Using the tested antibody panel we can reliably determine the EGFR protein expression in paraffin embedded (lung)cancer tissues. This work was supported by Ministry of Education (NKFP1a-0024–05). No significant financial relationships to disclose.

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Atypical Protein Kinase Cι Plays a Critical Role in Human Lung Cancer Cell Growth and Tumorigenicity

Journal of Biological Chemistry ◽

10.1074/jbc.m505402200 ◽

2005 ◽

Vol 280 (35) ◽

pp. 31109-31115 ◽

Cited By ~ 138

Author(s):

Roderick P. Regala ◽

Capella Weems ◽

Lee Jamieson ◽

John A. Copland ◽

E. Aubrey Thompson ◽

...

Keyword(s):

Lung Cancer ◽

Protein Kinase ◽

Cell Growth ◽

Cancer Cell ◽

Human Lung ◽

Critical Role ◽

Human Lung Cancer ◽

Lung Cancer Cell ◽

Cancer Cell Growth ◽

Human Lung Cancer Cell

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FAM83A-AS1 Promotes Tumor Progression Through MET Signaling in Lung Adenocarcinoma

10.21203/rs.3.rs-616083/v1 ◽

2021 ◽

Author(s):

Shengbin Bai ◽

Huijie Zhao ◽

Xaofei Zeng ◽

Baoyue Lin ◽

Yinghan Wang ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Functional Studies ◽

Cycle Arrest ◽

Elevated Expression ◽

Lung Cancer Therapy ◽

Prognosis Marker ◽

Cancer Tissues

Abstract Background Studies demonstrate that long non-coding RNAs (lncRNAs) play critical roles in the occurrence and development of cancer. However, many of the molecular mechanisms underlying lncRNAs role in this process remains unclear. Methods Here, we analyzed lncRNA expression in lung cancer tissues based on RNA-Seq analysis and found that lncRNA FAM83A-AS1 was one of the top up-regulated lncRNAs in lung adenocarcinoma and elevated expression of FAM83A-AS1 was significantly associated with poor patient survival. We validated these results using RT-PCR and an independent cohort of lung cancer. Results Functional studies indicated that knockdown of FAM83A-AS1 decreased cell proliferation, colony formation, migration and invasion in H1299 and H838 lung cancer cells. Knockdown of FAM83A-AS1 induced the autophagy and cell cycle arrest at G2. Mechanistically, we found that MET, p62 and phosphor S6K proteins were decreased upon FAM83A-AS1 knockdown. Conclusion In conclusion, FAM83A-AS1 may have potential as a diagnosis/prognosis marker and its oncogenic role could lead to potential targeting for lung cancer therapy.

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