The 1-Acyl-Glycerol-3-Phosphate AcylTransferase enzymes (AGPATs) is an emerging class of enzymes, and the AGPAT2 member is a potential prognostic/diagnostic marker for different tumors. AGPAT2 is up-regulated in several tumors and its increased expression/activity correlates with tumor aggressiveness. AGPAT2, also known as LysoPhosphatidic Acid AcylTransferase-? (LPAAT?), catalyses the acylation of lysophosphatidic acid to form phosphatidic acid, a phospholipid precursor involved in membrane transport and signalling for cell survival, proliferation and tumor progression1. Alteration in phospholipid membrane composition and enhanced cellular secretion are associated to tumor progression and migration/invasion. Indeed, during tumorigenesis the secreted factors of cancer cells are key actors in setting the microenvironment that leads to tumor progression. In addition to AGPAT2, also AGPAT3, 4, 8 and 11 are up-regulated in cancer cells. AGPAT4, like AGPAT2, is a LPAAT enzyme, and we have identified AGPAT4 as an important controller of secretion in cancer cells2. AGPAT4 expression/activity increases in prostate cancer, and this correlates with enhanced tumor aggressiveness. Conversely, its depletion impairs cells migration. However, the role of AGPATs in the exocytic pathways that drive tumor progression and migration/invasion remains unknown. We performed a proteomic approach to identify, in a sensitive, and at high-resolution manner, factors differentially secreted in the conditioned medium of prostate cancer versus non-cancer cells, by LC-MS/MS. Then, we have used the same differential proteomic approach to identify among these cancer-specific secreted factors those with reduced secretion under AGPAT4 depletion. Among them, we have found the human Growth Hormone and the membrane type 1- and type 9-matrix metalloproteases3,4, which are all involved in invasion/migration. The role of the identified AGPAT4-dependent cancer-secreted factors in tumor invasion/migration are under investigation.
The Lysophosphatidic acid acyltransferase (LPAATs) enzymes and their role in membrane transport alterations in cancer
Corda D;Luini A;Valente C
2017
Abstract
The 1-Acyl-Glycerol-3-Phosphate AcylTransferase enzymes (AGPATs) is an emerging class of enzymes, and the AGPAT2 member is a potential prognostic/diagnostic marker for different tumors. AGPAT2 is up-regulated in several tumors and its increased expression/activity correlates with tumor aggressiveness. AGPAT2, also known as LysoPhosphatidic Acid AcylTransferase-? (LPAAT?), catalyses the acylation of lysophosphatidic acid to form phosphatidic acid, a phospholipid precursor involved in membrane transport and signalling for cell survival, proliferation and tumor progression1. Alteration in phospholipid membrane composition and enhanced cellular secretion are associated to tumor progression and migration/invasion. Indeed, during tumorigenesis the secreted factors of cancer cells are key actors in setting the microenvironment that leads to tumor progression. In addition to AGPAT2, also AGPAT3, 4, 8 and 11 are up-regulated in cancer cells. AGPAT4, like AGPAT2, is a LPAAT enzyme, and we have identified AGPAT4 as an important controller of secretion in cancer cells2. AGPAT4 expression/activity increases in prostate cancer, and this correlates with enhanced tumor aggressiveness. Conversely, its depletion impairs cells migration. However, the role of AGPATs in the exocytic pathways that drive tumor progression and migration/invasion remains unknown. We performed a proteomic approach to identify, in a sensitive, and at high-resolution manner, factors differentially secreted in the conditioned medium of prostate cancer versus non-cancer cells, by LC-MS/MS. Then, we have used the same differential proteomic approach to identify among these cancer-specific secreted factors those with reduced secretion under AGPAT4 depletion. Among them, we have found the human Growth Hormone and the membrane type 1- and type 9-matrix metalloproteases3,4, which are all involved in invasion/migration. The role of the identified AGPAT4-dependent cancer-secreted factors in tumor invasion/migration are under investigation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
