Non-Cell Autonomous or Secretory Tumor Suppression

Many malignancies result from deletions or loss‐of‐function mutations in one or more tumor suppressor genes, the products of which curb unrestrained growth or induce cell death in those with dysregulated proliferative capacities. Most tumor suppressors act in a cell autonomous manner, and only very...

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Bibliographic Details
Published in:Journal of cellular physiology 2014-10, Vol.229 (10), p.1346-1352
Main Authors: Chua, Christelle En Lin, Chan, Shu Ning, Tang, Bor Luen
Format: Article
Language:English
Subjects:
Animals
Cell Death
Cell Proliferation
Humans
Mutation
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Neoplasms - secretion
Paracrine Communication
Signal Transduction
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
Tumor Suppressor Proteins - secretion
Tumors
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Summary:Many malignancies result from deletions or loss‐of‐function mutations in one or more tumor suppressor genes, the products of which curb unrestrained growth or induce cell death in those with dysregulated proliferative capacities. Most tumor suppressors act in a cell autonomous manner, and only very few proteins are shown to exert a non‐cell autonomous tumor suppressor function on other cells. Examples of these include members of the secreted frizzled‐related protein (SFRP) family and the secreted protein acidic and rich in cysteine (SPARC)‐related proteins. Very recent findings have, however, considerably expanded our appreciation of non‐cell autonomous tumor suppressor functions. Broadly, this may occur in two ways. Intracellular tumor suppressor proteins within cells could in principle inhibit aberrant growth of neighboring cells by conditioning an antitumor microenvironment through secreted factors. This is demonstrated by an apparent non‐cell autonomous tumor suppressing property of p53. On the other hand, a tumor suppressor produced by a cell may be secreted extracellularly, and taken up by another cell with its activity intact. Intriguingly, this has been recently shown to occur for the phosphatase and tensin homolog (PTEN) by both conventional and unconventional modes of secretion. These recent findings would aid the development of therapeutic strategies that seek to reinstate tumor suppression activity in therapeutically recalcitrant tumor cells, which have lost it in the first place. J. Cell. Physiol. 229: 1346–1352, 2014. © 2014 Wiley Periodicals, Inc.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.24574