TY - JOUR
T1 - Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer
AU - Sun, H.
AU - Jiang, L.
AU - Luo, X.
AU - Jin, W.
AU - He, Q.
AU - An, J.
AU - Lui, K.
AU - Shi, J.
AU - Rong, R.
AU - Su, W.
AU - Lucchesi, C.
AU - Liu, Y.
AU - Sheikh, M. S.
AU - Huang, Y.
N1 - Funding Information:
This work was supported by NIH Grants DK062136 and CA121850 to YH.
PY - 2013/1/10
Y1 - 2013/1/10
N2 - 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.
AB - 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.
KW - Akt
KW - colorectal cancer
KW - gene expression
KW - monoglyceride lipase
KW - phosphatidylinositides
UR - http://www.scopus.com/inward/record.url?scp=84872188934&partnerID=8YFLogxK
U2 - 10.1038/onc.2012.34
DO - 10.1038/onc.2012.34
M3 - Article
C2 - 22349814
AN - SCOPUS:84872188934
SN - 0950-9232
VL - 32
SP - 234
EP - 241
JO - Oncogene
JF - Oncogene
IS - 2
ER -
