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

Author

Jeanine L. Van Nostrand, Alice Brisac, Richard Luong, Stephano S. Mello, Laura D. Attardi, and Suzanne B.R. Jacobs

Subjects
Lung Neoplasms, Biology, medicine.disease_cause, Bioinformatics, Article, Proto-Oncogene Proteins p21(ras), Mice, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Conditional gene knockout, Gene Order, medicine, Autophagy, Animals, Humans, Lung cancer, Gene, Cell Proliferation, Mice, Knockout, Gene knockdown, TOR Serine-Threonine Kinases, Cancer, medicine.disease, respiratory tract diseases, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Cell Transformation, Neoplastic, Oncology, Apoptosis, Genetic Loci, Gene Targeting, Cancer research, Female, Non small cell, Tumor Suppressor Protein p53, Carcinogenesis, Apoptosis Regulatory Proteins, Energy Metabolism
Abstract

Although p53 transcriptional activation potential is critical for its ability to suppress cancer, the specific target genes involved in tumor suppression remain unclear. SIVA is a p53 target gene essential for p53-dependent apoptosis, although it can also promote proliferation through inhibition of p53 in some settings. Thus, the role of SIVA in tumorigenesis remains unclear. Here, we seek to define the contribution of SIVA to tumorigenesis by generating Siva conditional knockout mice. Surprisingly, we find that SIVA loss inhibits non–small cell lung cancer (NSCLC) development, suggesting that SIVA facilitates tumorigenesis. Similarly, SIVA knockdown in mouse and human NSCLC cell lines decreases proliferation and transformation. Consistent with this protumorigenic role for SIVA, high-level SIVA expression correlates with reduced NSCLC patient survival. SIVA acts independently of p53 and, instead, stimulates mTOR signaling and metabolism in NSCLC cells. Thus, SIVA enables tumorigenesis in a p53-independent manner, revealing a potential new cancer therapy target. Significance: These findings collectively reveal a novel role for the p53 target gene SIVA both in regulating metabolism and in enabling tumorigenesis, independently of p53. Importantly, these studies further identify SIVA as a new prognostic marker and as a potential target for NSCLC cancer therapy. Cancer Discov; 5(6); 622–35. ©2015 AACR. See related commentary by Resnick-Silverman and Manfredi, p. 581 This article is highlighted in the In This Issue feature, p. 565

Published
2014

8. Resting Places : The Burial Sites of More Than 14,000 Famous Persons, 3d Ed.

Author

Scott Wilson and Scott Wilson

Subjects
Celebrities--Tombs--Dictionaries, Celebrities--Biography--Dictionaries
Abstract

In its third edition, this massive reference work lists the final resting places of more than 14,000 people from a wide range of fields, including politics, the military, the arts, crime, sports and popular culture. Many entries are new to this edition. Each listing provides birth and death dates, a brief summary of the subject's claim to fame and their burial site location or as much as is known. Grave location within a cemetery is provided in many cases, as well as places of cremation and sites where ashes were scattered. Source information is provided.

Published
2013

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