Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo

Oncogenic KRAS mutations occur in approximately 30% of human lung adenocarcinoma. Despite tremendous effort over the past several decades, oncogenic KRAS-driven lung cancer remains difficult to treat, and our understanding of the positive and negative regulators of RAS signaling is incomplete. To uncover and corroborate the functional impact of diverse KRAS-interacting proteins on lung cancer growth in vivo, we integrate somatic CRISPR/Cas9-based genome editing in genetically engineered mouse models with tumor barcoding and high-throughput barcode sequencing (Tuba-seq). Through a series of in vivo CRISPR/Cas9 screens, we identified HRAS and NRAS as key suppressors of KRASG12D-driven lung tumor growth in vivo and confirmed these effects in oncogenic KRAS-driven human lung cancer cell lines. Mechanistically, we find that these RAS paralogs interact with oncogenic KRASG12D, suppress KRASG12D-KRASG12D interaction, and reduce downstream ERK signaling. Patient-derived mutations HRAST50M and HRASR123C partially abolished this effect. Comparison of the tumor-suppressive effects of HRAS and NRAS in KRASG12D- and BRAFV600E-driven lung cancer models confirmed that these RAS paralogs are specific suppressors of oncogenic KRAS-driven lung cancer in vivo. Our study outlines a technological avenue to specifically uncover positive and negative regulators of oncogenic KRAS-driven cancer in a multiplexed manner and highlights the role of RAS paralog imbalance in oncogenic KRAS-driven cancers.

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The natural human monoclonal IgM antibody LM-1 inhibits human lung cancer growth in vitro and in vivo

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.7347 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 7347-7347

Author(s):

S. Brändlein ◽

F. Hensel ◽

E. Wozniak ◽

H.-K. Müller-Hermelink ◽

H. P. Vollmers

Keyword(s):

Lung Cancer ◽

Human Lung ◽

Human Lung Cancer ◽

Cancer Growth ◽

Igm Antibody

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POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01476-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ronggang Luo ◽

Yi Zhuo ◽

Quan Du ◽

Rendong Xiao

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

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Bicistronic transfer of CDKN2A and p53 culminates in collaborative killing of human lung cancer cells in vitro and in vivo

Gene Therapy ◽

10.1038/s41434-019-0096-1 ◽

2019 ◽

Vol 27 (1-2) ◽

pp. 51-61

Author(s):

Juliana G. Xande ◽

Ana P. Dias ◽

Rodrigo E. Tamura ◽

Mario C. Cruz ◽

Bárbara Brito ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Human Lung Cancer Cells

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Effect of Compound K, a Metabolite of Ginseng Saponin, Combined with γ-Ray Radiation in Human Lung Cancer Cells in Vitro and in Vivo

Journal of Agricultural and Food Chemistry ◽

10.1021/jf900331g ◽

2009 ◽

Vol 57 (13) ◽

pp. 5777-5782 ◽

Cited By ~ 83

Author(s):

Sungwook Chae ◽

Kyoung Ah Kang ◽

Weon Young Chang ◽

Min Jung Kim ◽

Su Jae Lee ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Human Lung Cancer ◽

Compound K ◽

Ginseng Saponin ◽

Human Lung Cancer Cells ◽

Γ Ray

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Novel ferrocenyl-containingN-acetyl-2-pyrazolines inhibitin vitroangiogenesis and human lung cancer growth by interfering with F-actin stress fiber polimeryzation

Drug and Chemical Toxicology ◽

10.3109/01480545.2013.776579 ◽

2013 ◽

Vol 36 (4) ◽

pp. 484-495 ◽

Cited By ~ 14

Author(s):

Rakibe Beklem Bostancıoğlu ◽

Seda Demirel ◽

Günseli Turgut Cin ◽

Ayse Tansu Koparal

Keyword(s):

Lung Cancer ◽

Human Lung ◽

Stress Fiber ◽

Human Lung Cancer ◽

Cancer Growth ◽

Actin Stress Fiber

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The Marine Dinoflagellate Alexandrium minutum Activates a Mitophagic Pathway in Human Lung Cancer Cells

Marine Drugs ◽

10.3390/md16120502 ◽

2018 ◽

Vol 16 (12) ◽

pp. 502 ◽

Cited By ~ 6

Author(s):

Christian Galasso ◽

Genoveffa Nuzzo ◽

Christophe Brunet ◽

Adrianna Ianora ◽

Angela Sardo ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Water Soluble ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Normal Lung ◽

Alexandrium Minutum ◽

Human Lung Cancer Cells

Marine dinoflagellates are a valuable source of bioactive molecules. Many species produce cytotoxic compounds and some of these compounds have also been investigated for their anticancer potential. Here, we report the first investigation of the toxic dinoflagellate Alexandrium minutum as source of water-soluble compounds with antiproliferative activity against human lung cancer cells. A multi-step enrichment of the phenol–water extract yielded a bioactive fraction with specific antiproliferative effect (IC50 = 0.4 µg·mL−1) against the human lung adenocarcinoma cells (A549 cell line). Preliminary characterization of this material suggested the presence of glycoprotein with molecular weight above 20 kDa. Interestingly, this fraction did not exhibit any cytotoxicity against human normal lung fibroblasts (WI38). Differential gene expression analysis in A549 cancer cells suggested that the active fraction induces specific cell death, triggered by mitochondrial autophagy (mitophagy). In agreement with the cell viability results, gene expression data also showed that no mitophagic event was activated in normal cells WI38.

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