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The p53 Target Gene SIVA Enables Non-Small Cell Lung Cancer Development

Jeanine L Van Nostrand1, Alice Brisac2, Stephano S Mello1

  • 1Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.

Cancer Discovery
|March 28, 2015
PubMed
Abstract

Insights

The tumor suppressor p53 has target genes crucial for its function. SIVA, a p53 target gene, surprisingly promotes non-small cell lung cancer (NSCLC) development and progression, independent of p53.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The tumor suppressor function of p53 is critical, but its specific target genes in tumor suppression are not fully understood.
  • SIVA, a p53 target gene, has a dual role: promoting apoptosis but also potentially inhibiting p53 to drive proliferation, making its role in tumorigenesis unclear.

Purpose of the Study:

  • To elucidate the contribution of SIVA to tumorigenesis by generating Siva conditional knockout mice.
  • To investigate the role of SIVA in non-small cell lung cancer (NSCLC) development and progression.

Main Methods:

  • Generation of Siva conditional knockout mice.
  • SIVA knockdown in mouse and human NSCLC cell lines.
  • Analysis of NSCLC cell proliferation, transformation, and patient survival data.
  • Investigation of SIVA's signaling pathways, including mTOR and metabolism.

Main Results:

  • SIVA loss inhibited non-small cell lung cancer (NSCLC) development in mice.
  • SIVA knockdown decreased proliferation and transformation in NSCLC cell lines.
  • High SIVA expression correlated with reduced NSCLC patient survival.
  • SIVA promotes tumorigenesis independently of p53 by stimulating mTOR signaling and metabolism.

Conclusions:

  • SIVA plays a protumorigenic role in NSCLC, independent of p53.
  • SIVA regulates metabolism and enables tumorigenesis, identifying it as a potential therapeutic target and prognostic marker for NSCLC.

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