Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma

Hynds, Robert E.; Janes, Sam M.

doi:10.1158/1940-6207.capr-17-0202

Cited by 20 publications

(17 citation statements)

References 11 publications

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“…The results confirm that 16HBE‐T cells develop the characteristics of LSUC consistently with data from previous epidemiological and in vitro studies 41–43 . It is also well‐known that LUSC has a tendency to occur in the bronchi, and the 16HBE used in our in vitro experiments is an immortalized cell constructed from human normal bronchial epithelial cells 44,45 . Consequently, when it is induced by BPDE to become cancerous, it is more likely to differentiate into a phenotype of LUSC.…”

Section: Discussionsupporting

confidence: 88%

Benzo[a]pyrene diol epoxide‐induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1‐derived circular RNA in pulmonary squamous cell carcinoma

Xiao

Cui

Zhang

et al. 2021

Molecular Carcinogenesis

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ERCC1 is a gene for repairing DNA damage whose function is related to carcinogenic‐induced tumorigenesis and the effectiveness of platinum therapies. Circular RNAs (circRNAs) are products of posttranscriptional regulation with pleiotropic effects on the pathogenesis of lung cancer. We aim to identify that specific circRNAs derived from ERCC1 can regulate key biological processes involved in the development of lung cancer. We performed bioinformatics analysis, in vitro experiments, and analyzed clinical samples, to determine the biological features of a certain ERCC1‐derived circRNA termed as hsa_circ_0051488 in benzo[a]pyrene diol epoxide‐induced malignant transformed cell and lung cancer cell. The well‐established model of transformed cells provided an ideal platform for analyzing the molecular characteristics of this circRNA in the malignant transformation of lung epithelial cell, which supports that hsa_circ_0051488 functions in the onset and growth of lung squamous cell carcinoma (LUSC). Further analysis indicates that the absence of hsa_circ_0051488 promoted the proliferation of cells with the malignant phenotype. Extensive experiments confirm that hsa_circ_0051488 is present in the cytoplasm and functioned as a competing endogenous RNA. In particular, hsa_circ_0051488 binds to mir‐6717‐5p, thereby modulating the expression of SATB2 gene, a lung cancer suppressor. Furthermore, our in silico experiments indicate that SATB2 can inhibit multiple tumor pathways and its expression positively correlated with the tumor suppressor gene CRMP1. These findings suggest a possible regulatory mechanism of hsa_circ_0051488 in LUSC, and that the newly discovered hsa_circ_0051488/miR‐6717‐5p/SATB2 axis may be a potential route for therapeutic intervention of LUSC.

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Section: Discussionsupporting

confidence: 88%

Benzo[a]pyrene diol epoxide‐induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1‐derived circular RNA in pulmonary squamous cell carcinoma

Xiao

Cui

Zhang

et al. 2021

Molecular Carcinogenesis

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“…[ 1 , 2 , 3 ] Lung adenocarcinoma has been postulated to originate from club cells, AT2 cells, or BASCs, while squamous cell carcinomas likely arise from basal cells. [ 4 , 5 , 6 ] Experimental models have shown that given different oncogenes, lung cells can be more or less “fit” to form fully malignant lesions. [ 7 , 8 , 9 ] However, the cellular origins for the majority of lung cancers have not been clarified yet.…”

Section: Introductionmentioning

confidence: 99%

Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy

et al. 2021

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Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first-and second-generation TKIs, third-generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR-driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the EGFR T790M/L858R mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells or bronchioalveolar stem cells, but not basal cells or club cells of the trachea. It is also demonstrated that these clones are able to retain their epigenetic differences through passaging orthotopically in mice and crucially that they have distinct drug vulnerabilities. This work serves as a blueprint for exploring how epigenetics can be used to stratify patients for precision medicine decisions.

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“…Basal cells are progenitor cells closely associated with the basal lamina that maintain airway homeostasis. Basal cells are considered the candidate cell of origin in lung SqCC [6]. Although LUAD sometimes exhibits features of airway basal cells, there is no evidence that these cells can be its cell of origin [7].…”

Section: Introductionmentioning

confidence: 99%

Alveolar progenitor cells and the origin of lung cancer

2020

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Lung Cancer is the leading cause of cancer-related deaths worldwide. This is mainly due to late diagnosis and therefore advanced stage of the disease. Understanding the cell of origin of cancer and the processes that lead to its transformation will allow for earlier diagnosis and more accurate prediction of tumour type, ultimately leading to better treatments and lower patient morbidity. In this review, we focus on alveolar type 2 (AT2) cells as the cell of origin of lung adenocarcinoma (LUAD), the most common type of lung cancer. We first elaborate on the different oncogenes that are associated with LUAD and other lung cancers. After, we lay out in detail what is known about AT2 biology, to further delve into AT2 cells as cell of origin for adenocarcinoma. Understanding the precursors of LUAD and identifying the molecular changes during its progression will allow for earlier detection and better molecular targeting of the disease in early stages.

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Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma

Cited by 20 publications

References 11 publications

Benzo[a]pyrene diol epoxide‐induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1‐derived circular RNA in pulmonary squamous cell carcinoma

Benzo[a]pyrene diol epoxide‐induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1‐derived circular RNA in pulmonary squamous cell carcinoma

Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy

Alveolar progenitor cells and the origin of lung cancer

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