机构：[1]Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry ofEducation, Department of Pathophysiology, Shanghai Jiao Tong UniversitySchool of Medicine, Shanghai, China[2]Shanghai Pulmonary Hospital Affiliatedto Tongji University School of Medicine, Shanghai, China[3]Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao TongUniversity School of Medicine, Shanghai, China[4]Precision Medicine Center forRefractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University,Shanghai, China[5]Department of Laboratory Medicine, Shanghai East Hospital,Tongji University School of Medicine, Shanghai, China[6]Translation MedicineCenter, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[7]Department of Pathology, Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai, China[8]Department of Oral and Maxillofacial–Head and Neck Oncology, NinthPeople’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai,China[9]Department of Respiratory Medicine, the Second Affiliated Hospital,Dalian Medical University, Dalian, China[10]Department of Pathology, KunmingMedical University, Kunming, China[11]Yantai Peninsular Cancer Center, BinzhouMedical University, Yantai, China[12]Medical Research Institute, Binzhou MedicalUniversity Hospital, Binzhou, China[13]Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky College of Medicine,Lexington, Kentucky[14]Department of Thoracic Surgery, Shanghai Chest Hospital,Shanghai Jiao Tong University, Shanghai, China[15]Institutes of Biology andMedical Science, Soochow University Medical College, Suzhou, China
While initiation is established as a critical step in tumorigenesis, the identity of the cell-of-origin for lung adenocarcinoma and the mechanism controlling susceptibility to initiation remain elusive. Here we show that lung tumor suppressor Gprc5a-knockout (KO) mice are susceptible to initiation of lung tumorigenesis. Bronchioalveolar stem cells (BASC) and alveolar type 2 (AT2) cells were aberrantly expanded in Gprc5a-KO mouse lungs compared to those in wild-type (WT) mice, suggesting that Gprc5a-KO might confer susceptibility to initiation by increasing the cell of origin in mouse lungs. BASCs from Gprc5a-KO mice (KO-BASCs) exhibited significantly increased stemness and self-renewal potential and reduced differentiation capacity compared to BASCs from WT mice (WT-BASCs). AT2 cells did not possess self-renewal potential regardless of Gprc5a status. KO-BASCs expressed a stem-like gene profile with upregulated Abcg2, EGFR, and NF-κB signaling compared to WT-BASCs. Blockade of EGFR and NF-κB signaling inhibited both expansion of BASC and AT2 cells and lung tumorigenesis. Abcg2 was expressed in active KO-BASCs as well as in lung tumor cells but not in quiescent WT-BASCs or AT2 cells, supporting that lung adenocarcinoma cells are derived from Abcg2-positive KO-BASCs (active). Taken together, Gprc5a deletion leads to expansion of active BASCs via dysregulated EGFR and NF-κB signaling that confers susceptibility to initiation of lung tumorigenesis, marking Abcg2-positive BASCs as candidate cell-of-origin for lung adenocarcinoma.
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外文
PubmedID：
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出版当年[2021]版：
大类|1 区医学
小类|1 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|2 区肿瘤学
第一作者：
第一作者机构：[1]Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry ofEducation, Department of Pathophysiology, Shanghai Jiao Tong UniversitySchool of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry ofEducation, Department of Pathophysiology, Shanghai Jiao Tong UniversitySchool of Medicine, Shanghai, China[3]Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao TongUniversity School of Medicine, Shanghai, China[11]Yantai Peninsular Cancer Center, BinzhouMedical University, Yantai, China[12]Medical Research Institute, Binzhou MedicalUniversity Hospital, Binzhou, China[13]Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky College of Medicine,Lexington, Kentucky[*1]Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256600, China[*2]Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536.
推荐引用方式(GB/T 7714)：
Yin Huijing,Jing Bo,Xu Dongliang,et al.Identification of Active Bronchioalveolar Stem Cells as the Cell-of-Origin in Lung Adenocarcinoma.[J].Cancer research.2022,doi:10.1158/0008-5472.CAN-21-2445.
APA：
Yin Huijing,Jing Bo,Xu Dongliang,Guo Wenzheng,Sun Beibei...&Deng Jiong.(2022).Identification of Active Bronchioalveolar Stem Cells as the Cell-of-Origin in Lung Adenocarcinoma..Cancer research,,
MLA：
Yin Huijing,et al."Identification of Active Bronchioalveolar Stem Cells as the Cell-of-Origin in Lung Adenocarcinoma.".Cancer research .(2022)
医学