4.3 Article

SPANXA suppresses EMT by inhibiting c-JUN/SNAI2 signaling in lung adenocarcinoma

Journal

ONCOTARGET
Volume 7, Issue 28, Pages 44417-44429

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10088

Keywords

SPANX family; AP-1; SLUG; E-cadherin; metastasis

Funding

  1. Ministry of Science and Technology, Taiwan, R.O.C [NSC98-2314-B-002-120-MY3, NSC 102-2911-I-002-303, MOST103-2911-I-002-303, MOST104-2911-I-002-302]
  2. MIB, Institute of Statistical Science, Academia Sinica [5202402010-6]

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SPANXA (Sperm Protein Associated with the Nucleus on the X-chromosome, family members A1/A2) acts as a cancer-testis antigen expressed in normal testes, but dysregulated in various tumors. We found that SPANXA is highly expressed in low-invasive CL1-0 cells compared with isogenous high-invasive CL1-5 cells. SPANXA was preferably expressed in tumor tissues and associated with the prolonged survival of lung adenocarcinomas. SPANXA suppressed the invasion and metastasis of lung cancer cells in vitro and in vivo. By the expression microarray and pathway analysis, we found that the SPANXA-altered genes were enriched in the epithelial-mesenchymal transition (EMT) pathway. SPANXA reduced SNAI2 expression resulted in up-regulating E-cadherin. c-JUN acts as the positive-regulator of EMT. Silencing SPANXA increased c-JUN mRNA expression and blockage of c-JUN led to SNAI2 down-regulation. Our results clearly characterized SPANXA as an EMT inhibitor by suppressing c-JUN-SNAI2 axis in lung adenocarcinoma.

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