Numb has distinct function in lung adenocarcinoma and squamous cell carcinoma
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Hajime Kikuchi1, Jun Sakakibara-Konishi1, Megumi Furuta1, Eiki Kikuchi1, Junko Kikuchi1, Satoshi Oizumi2, Yasuhiro Hida3, Kichizo Kaga3, Ichiro Kinoshita4, Hirotoshi Dosaka-Akita4 and Masaharu Nishimura1
1Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
2Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan
3Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine, Hokkaido University, Sapporo, Japan
4Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Jun Sakakibara-Konishi, email: [email protected]
Keywords: Numb; Notch1; non-small cell lung cancer; adenocarcinoma; squamous cell carcinoma
Received: November 16, 2017 Accepted: May 21, 2018 Published: June 29, 2018
Some reports suggest that Numb is a potential tumor suppressor. However, its role in non-small cell lung cancer remains unclear. Non-small cell lung cancer comprises two major histological subtypes, adenocarcinoma and squamous cell carcinoma. To investigate the role of Numb in tumorigenesis of lung adenocarcinoma and squamous cell carcinoma, we firstly performed loss-of-function and gain-of-function assays. Moreover, Numb expression was investigated in surgically resected lung adenocarcinoma and squamous cell carcinoma tissues by immunohistochemistry and correlations with prognosis were analyzed. Numb suppressed the proliferation, migration, and invasion of adenocarcinoma cells and inhibited Notch signaling and epithelial-mesenchymal transition in vitro. Numb overexpression also inhibited subcutaneous adenocarcinoma tumor growth. In contrast, Numb promoted the proliferation, migration, and invasion of squamous cell carcinoma cells, but did not induce any consistent changes in Notch signaling. High Numb expression was associated with favorable prognosis in patients with lung adenocarcinoma, but not in those with squamous cell carcinoma. Collectively, our data demonstrate that Numb plays distinct roles in lung adenocarcinoma and squamous cell carcinoma. In lung adenocarcinoma, Numb impairs tumor growth and inhibits the Notch pathway and epithelial-mesenchymal transition, whereas in lung squamous cell carcinoma it may promote proliferation.
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