ERRATUM to Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer: Epigenetic control of the RUNX2 P1 promoter

Lung cancer has a high mortality rate in men and women worldwide. Approximately 15% of diagnosed patients with this type of cancer do not exceed the 5-year survival rate. Unfortunately, diagnosis is established in advanced stages, where other tissues or organs can be affected. In recent years, lineage-specific transcription factors have been associated with a variety of cancers. One such transcription factor possibly regulating cancer is RUNX2, the master gene of early and late osteogenesis. In thyroid and prostate cancer, it has been reported that RUNX2 regulates expression of genes important in tumor cell migration and invasion. In this study, we report on RUNX2/ p57 overexpression in 16 patients with primary non-small cell lung cancer and/or metastatic lung cancer associated with H3K27Ac at P1 gene promoter region. In some patients, H3K4Me3 enrichment was also detected, in addition to WDR5, MLL2, MLL4, and UTX enzyme recruitment, members of the COMPASS-LIKE complex. Moreover, transforming growth factor-β induced RUNX2/ p57 overexpression and specific RUNX2 knockdown supported a role for RUNX2 in epithelial mesenchymal transition, which was demonstrated through loss of function assays in adenocarcinoma A549 lung cancer cell line. Furthermore, RUNX2 increased expression of epithelial mesenchymal transition genes VIMENTIN, TWIST1, and SNAIL1, which reflected increased migratory capacity in lung adenocarcinoma cells.

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ARHGAP10 inhibits the epithelial–mesenchymal transition of non-small cell lung cancer by inactivating PI3K/Akt/GSK3β signaling pathway

Cancer Cell International ◽

10.1186/s12935-021-02022-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lan-Lan Lin ◽

Fan Yang ◽

Dong-Huan Zhang ◽

Cong Hu ◽

Sheng Yang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Signaling Pathway ◽

Cell Lung Cancer ◽

Rho Gtpase ◽

Epithelial Mesenchymal Transition ◽

Essential Element ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition

Abstract Background Rho GTPase activating protein 10 (ARHGAP10) has been implicated as an essential element in multiple cellular process, including cell migration, adhesion and actin cytoskeleton dynamic reorganization. However, the correlation of ARHGAP10 expression with epithelial–mesenchymal transition (EMT) in lung cancer cells is unclear and remains to be elucidated. Herein, we investigated the relationship between the trait of ARHGAP10 and non-small cell lung cancer (NSCLC) pathological process. Methods Immunohistochemistry was conducted to evaluate the expression of ARHGAP10 in NSCLC tissues. CCK-8 assays, Transwell assays, scratch assays were applied to assess cell proliferation, invasion and migration. The expression levels of EMT biomarkers and active molecules involved in PI3K/Akt/GSK3β signaling pathway were examined through immunofluorescence and Western blot. Results ARHGAP10 was detected to be lower expression in NSCLC tissues compared with normal tissues from individuals. Moreover, overexpression of ARHGAP10 inhibited migratory and invasive potentials of A549 and NCI-H1299 cells. In addition, ARHGAP10 directly mediated the process of EMT via PI3K/Akt/GSK3β pathway. Meanwhile, activation of the signaling pathway of insulin-like growth factors-1 (IGF-1) reversed ARHGAP10 overexpression regulated EMT in NSCLC cells. Conclusion ARHGAP10 inhibits the epithelial–mesenchymal transition in NSCLC via PI3K/Akt/GSK3β signaling pathway, suggesting agonist of ARHGAP10 may be an optional remedy for NSCLC patients than traditional opioids.

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PP4R1 interacts with HMGA2 to promote non‐small‐cell lung cancer migration and metastasis via activating MAPK/ERK‐induced epithelial‐mesenchymal transition

Molecular Carcinogenesis ◽

10.1002/mc.23168 ◽

2020 ◽

Vol 59 (5) ◽

pp. 467-477

Author(s):

Bin Wang ◽

Lin‐Yue Pan ◽

Ning Kang ◽

Xiao‐Yong Shen

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Cancer Migration

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456 Involvement of Matrix Metalloproteinases in Epithelial-mesenchymal Transition and Metastasis of Small-cell Lung Cancer

European Journal of Cancer ◽

10.1016/s0959-8049(12)71129-2 ◽

2012 ◽

Vol 48 ◽

pp. S109

Author(s):

T.D. Ahrens ◽

A. Krohn ◽

M. Follo ◽

S. Wollner ◽

M. Burger

Keyword(s):

Lung Cancer ◽

Matrix Metalloproteinases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition

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Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000488166 ◽

2018 ◽

Vol 45 (6) ◽

pp. 2213-2224 ◽

Cited By ~ 19

Author(s):

Meng Zhao ◽

Yahui Liu ◽

Ran Liu ◽

Jin Qi ◽

Yongwang Hou ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

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