title: Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer.
abstract: Human monoglyceride lipase (MGL) is a recently identified lipase and very little is known about its regulation and function in cellular regulatory processes, particularly in context to human malignancy. In this study, we investigated the regulation and function of MGL in human cancer(s) and report that MGL expression was either absent or reduced in the majority of primary colorectal cancers. Immunohistochemical studies showed that reduction of MGL expression in the colorectal tumor tissues predominantly occurred in the cancerous epithelial cells. MGL was found to reside in the core surface of a cellular organelle named 'lipid body'. Furthermore, it was found to interact selectively with a number of phospholipids, including phosphatidic acid and phosphoinositol(3,4,5)P3, phosphoinositol(3,5)P2, phosphoinositol(3,4)P2 and several other phosphoinositides, and among all phosphoinositides analyzed, its interaction with PI(3,4,5)P3 was found to be the strongest. In addition, overexpression of MGL suppressed colony formation in tumor cell lines and knockdown of MGL resulted in increased Akt phosphorylation. Taken together, our results suggest that MGL plays a negative regulatory role in phosphatidylinositol-3 kinase/Akt signaling and tumor cell growth.
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: W
authors.initials: W
authors.lastname: Jin
authors.forename: Q
authors.initials: Q
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: An
authors.forename: K
authors.initials: K
authors.lastname: Lui
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.forename: R
authors.initials: R
authors.lastname: Rong
authors.forename: W
authors.initials: W
authors.lastname: Su
authors.forename: C
authors.initials: C
authors.lastname: Lucchesi
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: M S
authors.initials: MS
authors.lastname: Sheikh
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008994:Monoacylglycerol Lipases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction
chemical_list: D010712:Phosphatidic Acids; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D034741:RNA, Small Interfering; C106336:phosphatidylinositol 3,5-diphosphate; C118303:phosphoinositide-3,4,5-triphosphate; C118301:phosphoinositide-3,4-bisphosphate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D008994:Monoacylglycerol Lipases