15-Lipoxygenase-1 as a tumor suppressor gene in colon cancer: is the verdict in?
15-Lipoxygenase-1 (15-LOX-1) is an inducible and highly regulated enzyme in normal human cells that plays a key role in the production of lipid signaling mediators, such as 13-hydroxyoctadecadienoic acid (13-HODE) from linoleic acid. 15-LOX-1 significantly contributes to the resolution of inflammation and to the terminal differentiation of normal cells. 15-LOX-1 is downregulated in human colorectal polyps and cancers. Emerging data support a tumor suppressor role for 15-LOX-1, especially in colon cancer. These data indicate that 15-LOX-1 promotes various anti-tumorigenic events, including cell differentiation and apoptosis, and inhibits chronic inflammation, angiogenesis, and metastasis. The transcriptional repression of 15-LOX-1 in colon cancer cells is complex and involves multiple mechanisms (e.g., histone methylation, transcriptional repressor binding). Re-expression of 15-LOX-1 in colon cancer cells can function as an important therapeutic mechanism and could be further exploited to develop novel treatment approaches for this common cancer.
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sun
S
Il Lee
Xiangsheng
X
Zuo
Imad
I
Shureiqi
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D001093:Arachidonate 15-Lipoxygenase