title: SPOCK1 is a novel transforming growth factor-β target gene that regulates lung cancer cell epithelial-mesenchymal transition.
abstract: Lung cancer is the leading cause of cancer related death worldwide and the prognosis is still poor with 5-year survival of approximately 15%. Metastasis is the leading cause of death by cancer. Recent researches have demonstrated that epithelial-to-mesenchymal transition (EMT) plays a key role in the early process of metastasis of cancer cells. Here, we identified that SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) is a novel transforming growth factor-β1 (TGF-β) target gene that regulates lung cancer cell EMT. TGF-β has been reported as a major inductor of EMT. We observed that the expression of SPOCK1 in lung cancer tumor tissues is significantly higher than matched normal lung tissues. Moreover, the expression of SPOCK1 was also significantly higher in metastasis tumor tissues than non-metastasis tumor tissues. Levels of SPOCK1 mRNA were increased among patients with shorter disease-free survival times, indicating the potential role of SPOCK1 in lung cancer progression and metastasis. Silencing SPOCK1 expression with endoribonuclease-prepared small interfering RNA (esiRNA) in lung cells inhibits lung cancer cell growth, colony formation and invasion in vitro. Interestingly, ectopic expression of SPOCK1 in epithelial lung cancer cells induced EMT with increased expression of the mesenchymal marker Vimentin and decreased expression of epithelial marker E-cadherin. We also found that the expression of SPOCK1 was increased under treatment of TGF-β, indicating that SPOCK1 is a novel downstream target of TGF-β. Taken together, our study showed that SPOCK1 is a novel metastasis related biomarker in lung cancer and may be new diagnostic and therapeutic target for lung cancer.
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Miao
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongping
authors.initials: H
authors.lastname: Xia
authors.forename: Chengyun
authors.initials: C
authors.lastname: Yao
authors.forename: Hourong
authors.initials: H
authors.lastname: Cai
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
mesh_terms: D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009362:Neoplasm Metastasis; D011509:Proteoglycans / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D011509:Proteoglycans; C504369:SPOCK1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Epithelial–mesenchymal transition; Lung cancer; SPOCK1; Transforming growth factor-β