scholarly journals FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2-1-negative lung cancer

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Soledad A Camolotto ◽  
Shrivatsav Pattabiraman ◽  
Timothy L Mosbruger ◽  
Alex Jones ◽  
Veronika K Belova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Therapeutic Response ◽  
Human Lung ◽  
Adenosquamous Carcinoma ◽  
Alveolar Cells ◽  
In Vivo Recombination ◽  
Cellular Identity ◽  
Context Specific ◽  
Lung Adenocarcinomas

Changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments the growth of KRAS-driven lung adenocarcinoma and causes pulmonary to gastric transdifferentiation. Here, we show that the transcription factors FoxA1 and FoxA2 are required for initiation of mucinous NKX2-1-negative lung adenocarcinomas in the mouse and for activation of their gastric differentiation program. Foxa1/2 deletion severely impairs tumor initiation and causes a proximal shift in cellular identity, yielding tumors expressing markers of the squamocolumnar junction of the gastrointestinal tract. In contrast, we observe downregulation of FoxA1/2 expression in the squamous component of both murine and human lung adenosquamous carcinoma. Using sequential in vivo recombination, we find that FoxA1/2 loss in established KRAS-driven neoplasia originating from SPC-positive alveolar cells induces keratinizing squamous cell carcinomas. Thus, NKX2-1, FoxA1 and FoxA2 coordinately regulate the growth and identity of lung cancer in a context-specific manner.

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

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.

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

Gene Therapy ◽  
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

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

2009 ◽  
Vol 57 (13) ◽  
pp. 5777-5782 ◽  
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

Anti-proliferative activity of Bupleurum scrozonerifolium in A549 human lung cancer cells in vitro and in vivo

2005 ◽  
Vol 222 (2) ◽  
pp. 183-193 ◽  
Author(s):  
Yeung-Leung Cheng ◽  
Shih-Chun Lee ◽  
Shinn-Zong Lin ◽  
Wen-Liang Chang ◽  
Yi-Lin Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Proliferative Activity ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells

scholarly journals P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo

1996 ◽  
Vol 74 (12) ◽  
pp. 1929-1934 ◽  
Author(s):  
Y Abe ◽  
Y Ohnishi ◽  
M Yoshimura ◽  
E Ota ◽  
Y Ozeki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
P Glycoprotein ◽  
Human Lung Cancer Cells

scholarly journals In vitro and in vivo properties of CD133 expressing cells from human lung cancer cell lines

2013 ◽  
Vol 2 (1) ◽  
pp. 16 ◽  
Author(s):  
Ping Wang ◽  
Zhenhe Suo ◽  
Mengyu Wang ◽  
Hanne K Høifødt ◽  
Øystein Fodstad ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Lung ◽  
Cancer Cell Lines ◽  
Human Lung Cancer ◽  
Lung Cancer Cell ◽  
Human Lung Cancer Cell

scholarly journals EML4-ALK V3 drives cell migration through NEK9 and NEK7 kinases in non-small-cell lung cancer

2019 ◽  
Author(s):  
Laura O’Regan ◽  
Giancarlo Barone ◽  
Rozita Adib ◽  
Chang Gok Woo ◽  
Hui Jeong Jeong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Disease Progression ◽  
Therapeutic Response ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung ◽  
Constitutive Activation ◽  
Microtubule Stabilization ◽  
Lung Adenocarcinomas

ABSTRACTEML4-ALK is an oncogenic fusion present in ∼5% lung adenocarcinomas. However, distinct EML4-ALK variants differ in the length of the EML4 microtubule-associated protein encoded within the fusion and are associated with a poorly understood variability in disease progression and therapeutic response. Here, we show that EML4-ALK variant 3, which is linked to accelerated metastatic spread and worse patient outcome, causes microtubule stabilization, formation of extended cytoplasmic protrusions, loss of cell polarity and increased cell migration. Strikingly, this is dependent upon the NEK9 kinase that interacts with the N-terminal region of EML4. Overexpression of wild-type EML4, as well as constitutive activation of NEK9, also perturbs cell morphology and accelerates cell migration in a manner that requires the downstream kinase NEK7 but not ALK activity. Moreover, elevated NEK9 is associated in patients with EML4-ALK V3 expression, as well as reduced progression-free and overall survival. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through recruitment of NEK9 and NEK7 to increase cell migration and that this represents a novel actionable pathway that drives disease progression in lung cancer.

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