Effect of Lysophosphatidic Acid on Cell Migration and Its Relative Molecular Mechanisms_Journal of Biomedical Engineering

Authors：

LINChuanchuan , LIDuo , LIJiawen ,  SONGGuanbin

College of Bioengineering, Chongqing University, Chongqing 400044, China;

Corresponding author：

SONGGuanbin, Email: song9973@163.com

Keywords：

lysophosphatidic acid; lysophosphatidic acid receptor; cell migration; molecular mechanism

DOI：

10.7507/1001-5515.20160161

Video：

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Lysophosphatidic acid (LPA) is a pluripotent lipid mediator and acts via different G-protein-couple LPA receptors. LPA has significant effects on several cellular biological behaviours, such as cell migration, invasion, proliferation and differentiation, etc. Cell migration is essential for tumor progression, and vital for stem cell to repair injured tissues. Increasing evidences have demonstrated that LPA dramatically affects migration capacity of various cells, particularly cancer cells and stem cells. In this paper, we review the effect of LPA on migration of cancer cells and stem cells, and discuss the underlying mechanisms. A better understanding of this process will shed new light on tissue regeneration and the prevention of tumor progression.

Citation： LIN Chuanchuan, LI Duo, LI Jiawen, SONG Guanbin. Effect of Lysophosphatidic Acid on Cell Migration and Its Relative Molecular Mechanisms. Journal of Biomedical Engineering, 2016, 33(5): 1005-1010. doi: 10.7507/1001-5515.20160161 Copy

1.	STODDARD N C, CHUN J. Promising pharmacoloogical directions in the world of lysophosphatidic acid signaling[J]. Biomolecules & Therapeutics, 2015, 23(1):1-11.
2.	MUELLER P, YE S J, MORRIS A, et al. Lysophospholipid mediators in the vasculature[J]. Exp Cell Res, 2015, 333(2):190-194.
3.	LEBLANC R, PEYRUCHAUD O. New insights into the autotaxin/LPA axis in cancer development and metastasis[J]. Exp Cell Res, 2015, 333(2):183-189.
4.	D'ARRIGO P, SCOTTI M. Lysophospholipids:synthesis and biological aspects[J]. Curr Org Chem, 2013, 17(8):812-830.
5.	KANG S J, HAN J H, SONG S Y, et al. Lysophosphatidic acid increases the proliferation and migration of adipose-derived stem cells via the generation of reactive oxygen species[J]. Mol Med Rep, 2015, 12(4, A):5203-5210.
6.	TSUJIUCHI T, ARAKI M, HIRANE M, et al. Lysophosphatidic acid receptors in cancer pathobiology[J]. Histol Histopathol, 2014, 29(3):313-321.
7.	CHOI J W, HERR D R, NOGUCHI K, et al. LPA receptors:subtypes and biological actions[J]. Annu Rev Pharmacol Toxicol, 2010, 50(21):157-186.
8.	SHENG X, YUNG Y C, CHEN A, et al. Lysophosphatidic acid signalling in development[J]. Development, 2015, 142(8):1390-1395.
9.	AIKAWA S, HASHIMOTO T, KANO K, et al. Lysophosphatidic acid as a lipid mediator with multiple biological actions[J]. J Biochem, 2015, 157(7):81-89.
10.	YUNG Y C, STODDARD N C, CHUN J. LPA receptor signaling:pharmacology, physiology, and pathophysiology[J]. J Lipid Res, 2014, 55(7):1192-1214.
11.	WILLIER S, BUTT E, GRUNEWALD T G. Lysophosphatidic acid (LPA) signalling in cell migration and cancer invasion:A focussed review and analysis of LPA receptor gene expression on the basis of more than 1700 cancer microarrays[J]. Biol Cell, 2013, 105(8):317-333.
12.	CHOI J W, CHUN J. Lysophospholipids and their receptors in the central nervous system[J]. Biochim Biophys Acta, 2013, 1831(1):20-32.
13.	ISHII S, HIRANE M, FUKUSHIMA Kaori, et al. Diverse effects of LPA4, LPA5 and LPA6 on the activation of tumor progression in pancreatic cancer cells[J]. Biochem Biophys Res Commun, 2015, 461(1):59-64.
14.	ROLIN J, MAGHAZACHI A A. Effects of lysophospholipids on tumor microenvironment[J]. Cancer Microenviron, 2011, 4(3):393-403.
15.	MILLS G B, MOOLENAAR W H. The emerging role of lysophosphatidic acid in cancer[J]. Nat Rev Cancer, 2003, 3(8):582-591.
16.	BRADDOCK D T. Autotaxin and lipid signaling pathways as anticancer targets[J]. Curr Opin Investig Drugs, 2010, 11(6):629-637.
17.	JESIONOWSKA A, CECERSKA-HERYC E, MATOSZKA N A. Lysophosphatidic acid signaling in ovarian cancer[J]. J Recept Signal Transduct Res, 2015, 35(6):578-584.
18.	KATO K, YOSHIKAWA K, TANABE E, et al. Opposite roles of LPA1 and LPA3 on cell motile and invasive activities of pancreatic cancer cells[J]. Tumour Biol, 2012, 33(5):1739-1744.
19.	SOKOLOV E, EHEIM A L, AHRENS W A, et al. Lysophosphatidic acid receptor expression and function in human hepatocellular carcinoma[J]. J Surg Res, 2013, 180(1):104-113.
20.	ZUCKERMAN V, SOKOLOV E, SWET J H, et al. Expression and function of lysophophatidic acid receptors 1 and 3 in human hepatic cancer progenitor cells[J]. Oncotarget, 2015, 7(3):2951-2967.
21.	PARK S Y, JEONG K J, PANUPINTHU N, et al. Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression[J]. Oncogene, 2011, 30(11):1351-1359.
22.	DONG Yan, HIRANE M, ARAKI M, et al. Lysophosphatidic acid receptor-5 negatively regulates cell motile and invasive activities of human sarcoma cell lines[J]. Mol Cell Biochem, 2014, 393(1/2):17-22.
23.	YAP L F, VELAPASAMY S, LEE H M, et al. Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma[J]. J Pathol, 2015, 235(3):456-465.
24.	LEE Z, CHENG C T, ZHANG H, et al. Role of LPA4/p2y9/GPR23 in negative regulation of cell motility[J]. Mol Biol Cell, 2008, 19(12):5435-5445.
25.	RYU J M, HAN H J. Autotaxin-LPA axis regulates hMSC migration by adherent junction disruption and cytoskeletal rearrangement via LPAR1/3-dependent PKC/GSK3β/β-catenin and PKC/Rho GTPase pathways[J]. Stem Cells, 2015, 33(3):819-832.
26.	ESTIBALIZ G D, IVAN M, MARIA T, et al. Anatomical location of LPA1 activation and LPA phospholipid precursors in rodent and human brain[J]. J Neurochem, 2015, 134(11):471-485.
27.	BLACKBURN J, MANSELL J P. The emerging role of lysophosphatidic acid (LPA) in skeletal biology[J]. Bone, 2012, 50(3):756-762.
28.	PEBAY A, BONDER C S, PITSON S M. Stem cell regulation by lysophospholipids[J]. Prostaglandins Other Lipid Mediat, 2007, 84(3/4):83-97.
29.	VÁZQUEZ-VICTORIO G, GONZÁLEZ-ESPINOSA C, ESPINOSA-RIQUER Z P, et al. GPCRs and actin-cytoskeleton dynamics[J]. Methods Cell Biol, 2016, 132(9):165-188.
30.	DEVREOTES P, HORWITZ A R. Signaling networks that regulate cell migration[J]. Cold Spring Harb Perspect Biol, 2015, 7(8):a005959.
31.	JEONG K J, PARK S Y, CHO K H, et al. The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion[J]. Oncogene, 2012, 31(39):4279-4289.
32.	JEONG G, SHIN S H, SEO E J, et al. TAZ mediates lysophosphatidic acid-induced migration and proliferation of epithelial ovarian cancer cells[J]. Cell Physiol Biochem, 2013, 32(2):253-263.
33.	LI T T, ALEMAYEHU M, AZIZIYEH Adel-i, et al. Beta-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells[J]. Mol Cancer Res, 2009, 7(7):1064-1077.
34.	HU Hai, JUVEKAR A, LYSSIOTIS C A, et al. Phosphoinositide 3-Kinase regulates glycolysis through mobilization of aldolase from the actin cytoskeleton[J]. Cell, 2016, 164(3):433-446.
35.	ASRUM M, TJOMSLAND V, THORESEN G H, et al. PI3K is required for both basal and LPA-induced DNA synthesis in oral carcinoma cells[J]. J Oral Pathol Med, 2015, doi:10.1111/jop.12384.
36.	JONGSMA M, MATAS-RICO E, RZADKOWSKI A, et al. LPA is a chemorepellent for B16 melanoma cells:action through the cAMP-Elevating LPA(5) receptor[J]. PLoS One, 2011, 6(12):e29260.
37.	王法微, 王骐, 邓宇, 等.磷脂酶C基因家族研究进展[J].生物技术通报, 2014, 12(12):33-39.
38.	PARK S J, LEE K P, IM D S. Action and signaling of lysophosphatidylethanolamine in MDA-MB-231 breast cancer cells[J]. Biomol Ther (Seoul), 2014, 22(2):129-135.
39.	BRUSEVOLD I J, TVETERAAS I H, AASRUM M A, et al. Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells[J]. BMC Cancer, 2014, 14(12):1-16.
40.	WAYS D K, KUKOLY C A, DEVENTE J, et al. MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype[J]. J Clin Invest, 1995, 95(4):1906-1915.
41.	BURDYGA A, CONANT A, HAYNES L, et al. cAMP inhibits migration, ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells:effects of PKA and EPAC[J]. Biochim Biophys Acta, 2013, 1833(12):2664-2672.
42.	ZIMMERMAN N P, ROY I, HAUSER A D, et al. Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells[J]. Mol Carcinog, 2015, 54(3):203-215.
43.	WHETTON A D, LU Y, PIERCE A, et al. Lysophospholipids synergistically promote primitive hematopoietic cell chemotaxis via a mechanism involving Vav1[J]. Blood, 2003, 102(8):2798-2802.

1. STODDARD N C, CHUN J. Promising pharmacoloogical directions in the world of lysophosphatidic acid signaling[J]. Biomolecules & Therapeutics, 2015, 23(1):1-11.
2. MUELLER P, YE S J, MORRIS A, et al. Lysophospholipid mediators in the vasculature[J]. Exp Cell Res, 2015, 333(2):190-194.
3. LEBLANC R, PEYRUCHAUD O. New insights into the autotaxin/LPA axis in cancer development and metastasis[J]. Exp Cell Res, 2015, 333(2):183-189.
4. D'ARRIGO P, SCOTTI M. Lysophospholipids:synthesis and biological aspects[J]. Curr Org Chem, 2013, 17(8):812-830.
5. KANG S J, HAN J H, SONG S Y, et al. Lysophosphatidic acid increases the proliferation and migration of adipose-derived stem cells via the generation of reactive oxygen species[J]. Mol Med Rep, 2015, 12(4, A):5203-5210.
6. TSUJIUCHI T, ARAKI M, HIRANE M, et al. Lysophosphatidic acid receptors in cancer pathobiology[J]. Histol Histopathol, 2014, 29(3):313-321.
7. CHOI J W, HERR D R, NOGUCHI K, et al. LPA receptors:subtypes and biological actions[J]. Annu Rev Pharmacol Toxicol, 2010, 50(21):157-186.
8. SHENG X, YUNG Y C, CHEN A, et al. Lysophosphatidic acid signalling in development[J]. Development, 2015, 142(8):1390-1395.
9. AIKAWA S, HASHIMOTO T, KANO K, et al. Lysophosphatidic acid as a lipid mediator with multiple biological actions[J]. J Biochem, 2015, 157(7):81-89.
10. YUNG Y C, STODDARD N C, CHUN J. LPA receptor signaling:pharmacology, physiology, and pathophysiology[J]. J Lipid Res, 2014, 55(7):1192-1214.
11. WILLIER S, BUTT E, GRUNEWALD T G. Lysophosphatidic acid (LPA) signalling in cell migration and cancer invasion:A focussed review and analysis of LPA receptor gene expression on the basis of more than 1700 cancer microarrays[J]. Biol Cell, 2013, 105(8):317-333.
12. CHOI J W, CHUN J. Lysophospholipids and their receptors in the central nervous system[J]. Biochim Biophys Acta, 2013, 1831(1):20-32.
13. ISHII S, HIRANE M, FUKUSHIMA Kaori, et al. Diverse effects of LPA4, LPA5 and LPA6 on the activation of tumor progression in pancreatic cancer cells[J]. Biochem Biophys Res Commun, 2015, 461(1):59-64.
14. ROLIN J, MAGHAZACHI A A. Effects of lysophospholipids on tumor microenvironment[J]. Cancer Microenviron, 2011, 4(3):393-403.
15. MILLS G B, MOOLENAAR W H. The emerging role of lysophosphatidic acid in cancer[J]. Nat Rev Cancer, 2003, 3(8):582-591.
16. BRADDOCK D T. Autotaxin and lipid signaling pathways as anticancer targets[J]. Curr Opin Investig Drugs, 2010, 11(6):629-637.
17. JESIONOWSKA A, CECERSKA-HERYC E, MATOSZKA N A. Lysophosphatidic acid signaling in ovarian cancer[J]. J Recept Signal Transduct Res, 2015, 35(6):578-584.
18. KATO K, YOSHIKAWA K, TANABE E, et al. Opposite roles of LPA1 and LPA3 on cell motile and invasive activities of pancreatic cancer cells[J]. Tumour Biol, 2012, 33(5):1739-1744.
19. SOKOLOV E, EHEIM A L, AHRENS W A, et al. Lysophosphatidic acid receptor expression and function in human hepatocellular carcinoma[J]. J Surg Res, 2013, 180(1):104-113.
20. ZUCKERMAN V, SOKOLOV E, SWET J H, et al. Expression and function of lysophophatidic acid receptors 1 and 3 in human hepatic cancer progenitor cells[J]. Oncotarget, 2015, 7(3):2951-2967.
21. PARK S Y, JEONG K J, PANUPINTHU N, et al. Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression[J]. Oncogene, 2011, 30(11):1351-1359.
22. DONG Yan, HIRANE M, ARAKI M, et al. Lysophosphatidic acid receptor-5 negatively regulates cell motile and invasive activities of human sarcoma cell lines[J]. Mol Cell Biochem, 2014, 393(1/2):17-22.
23. YAP L F, VELAPASAMY S, LEE H M, et al. Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma[J]. J Pathol, 2015, 235(3):456-465.
24. LEE Z, CHENG C T, ZHANG H, et al. Role of LPA4/p2y9/GPR23 in negative regulation of cell motility[J]. Mol Biol Cell, 2008, 19(12):5435-5445.
25. RYU J M, HAN H J. Autotaxin-LPA axis regulates hMSC migration by adherent junction disruption and cytoskeletal rearrangement via LPAR1/3-dependent PKC/GSK3β/β-catenin and PKC/Rho GTPase pathways[J]. Stem Cells, 2015, 33(3):819-832.
26. ESTIBALIZ G D, IVAN M, MARIA T, et al. Anatomical location of LPA1 activation and LPA phospholipid precursors in rodent and human brain[J]. J Neurochem, 2015, 134(11):471-485.
27. BLACKBURN J, MANSELL J P. The emerging role of lysophosphatidic acid (LPA) in skeletal biology[J]. Bone, 2012, 50(3):756-762.
28. PEBAY A, BONDER C S, PITSON S M. Stem cell regulation by lysophospholipids[J]. Prostaglandins Other Lipid Mediat, 2007, 84(3/4):83-97.
29. VÁZQUEZ-VICTORIO G, GONZÁLEZ-ESPINOSA C, ESPINOSA-RIQUER Z P, et al. GPCRs and actin-cytoskeleton dynamics[J]. Methods Cell Biol, 2016, 132(9):165-188.
30. DEVREOTES P, HORWITZ A R. Signaling networks that regulate cell migration[J]. Cold Spring Harb Perspect Biol, 2015, 7(8):a005959.
31. JEONG K J, PARK S Y, CHO K H, et al. The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion[J]. Oncogene, 2012, 31(39):4279-4289.
32. JEONG G, SHIN S H, SEO E J, et al. TAZ mediates lysophosphatidic acid-induced migration and proliferation of epithelial ovarian cancer cells[J]. Cell Physiol Biochem, 2013, 32(2):253-263.
33. LI T T, ALEMAYEHU M, AZIZIYEH Adel-i, et al. Beta-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells[J]. Mol Cancer Res, 2009, 7(7):1064-1077.
34. HU Hai, JUVEKAR A, LYSSIOTIS C A, et al. Phosphoinositide 3-Kinase regulates glycolysis through mobilization of aldolase from the actin cytoskeleton[J]. Cell, 2016, 164(3):433-446.
35. ASRUM M, TJOMSLAND V, THORESEN G H, et al. PI3K is required for both basal and LPA-induced DNA synthesis in oral carcinoma cells[J]. J Oral Pathol Med, 2015, doi:10.1111/jop.12384.
36. JONGSMA M, MATAS-RICO E, RZADKOWSKI A, et al. LPA is a chemorepellent for B16 melanoma cells:action through the cAMP-Elevating LPA(5) receptor[J]. PLoS One, 2011, 6(12):e29260.
37. 王法微, 王骐, 邓宇, 等.磷脂酶C基因家族研究进展[J].生物技术通报, 2014, 12(12):33-39.
38. PARK S J, LEE K P, IM D S. Action and signaling of lysophosphatidylethanolamine in MDA-MB-231 breast cancer cells[J]. Biomol Ther (Seoul), 2014, 22(2):129-135.
39. BRUSEVOLD I J, TVETERAAS I H, AASRUM M A, et al. Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells[J]. BMC Cancer, 2014, 14(12):1-16.
40. WAYS D K, KUKOLY C A, DEVENTE J, et al. MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype[J]. J Clin Invest, 1995, 95(4):1906-1915.
41. BURDYGA A, CONANT A, HAYNES L, et al. cAMP inhibits migration, ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells:effects of PKA and EPAC[J]. Biochim Biophys Acta, 2013, 1833(12):2664-2672.
42. ZIMMERMAN N P, ROY I, HAUSER A D, et al. Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells[J]. Mol Carcinog, 2015, 54(3):203-215.
43. WHETTON A D, LU Y, PIERCE A, et al. Lysophospholipids synergistically promote primitive hematopoietic cell chemotaxis via a mechanism involving Vav1[J]. Blood, 2003, 102(8):2798-2802.

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