Tumor Biology

, Volume 37, Issue 2, pp 2597–2602 | Cite as

Overexpression of Gremlin promotes non-small cell lung cancer progression

  • Yunhong Yin
  • Yie Yang
  • Liyun Yang
  • Yan Yang
  • Chunyu Li
  • Xiao Liu
  • Yiqing Qu
Original Article


Lung cancer is the major cause of cancer-related death worldwide, and 80 % of them are non-small cell lung cancer (NSCLC) cases. Gremlin, a bone morphogenetic protein (BMP) antagonist, is overexpressed in various cancerous tissues; however, little is known about the roles of Gremlin in lung carcinogenesis, and it remains unclear whether Gremlin expression may associate with EGFR-TKI resistance. In this study, expression of Gremlin mRNA and protein in matched tumor and normal lung specimens are quantified by quantitative real-time PCR and western blot. The functional role of Gremlin in NSCLC cells was evaluated by interference RNA (siRNA). The effects of Silenced Gremlin on the resistant PC-9/GR cell line were investigated by proliferation and apoptosis analysis compared with control PC-9 cells. Our results found that Gremlin expression levels were higher in NSCLC tissues, and Gremlin was more highly expressed in PC-9/GR cells compared to PC-9 cells. Knocking down of Gremlin in PC-9/GR cells decreased cell proliferation and increased the expression of BMP7 protein. In addition, Gremlin silencing significantly potentiated apoptosis induced by gefitinib in PC-9/GR with Gremlin knockdown compared to PC-9 transfected with control shRNA, suggesting Gremlin contributes to gefitinib resistance in NSCLC. Gremlin might be explored as a candidate of therapeutic target for modulating EGFR-TKI sensitivity in NSCLC.


Lung cancer NSCLC Gremlin EGFR-TKI PC-9/GR cells Proliferation Apoptosis Chemoresistance 



This work is supported by the National Natural Science Foundation of China, 81372333, and the Science and Technology Foundation of Shandong Province, 2014GSF118084.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yunhong Yin
    • 1
  • Yie Yang
    • 2
  • Liyun Yang
    • 3
  • Yan Yang
    • 1
  • Chunyu Li
    • 1
  • Xiao Liu
    • 1
  • Yiqing Qu
    • 1
  1. 1.Department of Respiratory MedicineQilu Hospital of Shandong UniversityJinanChina
  2. 2.Clinical LaboratoryQianfoshan Hospital of Shandong ProvinceJinanChina
  3. 3.Yinan Branch of Qilu Hospital of Shandong UniversityYinanChina

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