title: SOSTDC1 is down-regulated in non-small cell lung cancer and contributes to cancer cell proliferation.
abstract: BACKGROUND
  Non-small cell lung cancer (NSCLC) is the most commonly diagnosed and fatal cancer worldwide. Sclerostin domain containing protein 1 (SOSTDC1) has been found to be tumor-suppressive in several types of cancers. However, the expression level and biological functions of SOSTDC1 in NSCLC remain unknown. Our current study aimed to identify the biological significance of SOSTDC1 in NSCLC.
  
  
  RESULTS
  We found that SOSTDC1 was significantly down-regulated in NSCLC. Moreover, patients with higher expression of SOSTDC1 had a significant better prognosis than those with lower SOSTDC1 expression. Ectopic expression of SOSTDC1 in NSCLC cell lines A549 and NCI-H520 could inhibit proliferation as shown by MTT, colony formation, soft agar and EdU incorporation assays in vitro. Furthermore, A549 cells stably expressing ectopic SOSTDC1 grew more slowly and formed smaller tumors than vector-control cells in vivo. Mechanistic studies demonstrated that SOSTDC1 over-expression led to increased p21Cip and p27Kip levels, thereby decreasing Rb phosphorylation status and E2F transcription activity.
  
  
  CONCLUSIONS
  SOSTDC1 is down-regulated in NSCLC, and its expression level is indicative of clinical outcome of patients with the disease. SOSTDC1 might represent a tumor suppressor through inhibiting the proliferation of NSCLC cells by regulating p21Cip and p27Kip, which in turn affects Rb-E2F signaling.
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.|Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 Guangdong China.
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
keywords: Non-small cell lung cancer; Proliferation; SOSTDC1; p21Cip; p27Kip