A Novel Interaction between Chemokine and Phosphoinositide Signaling in Metastatic Prostate Cancer
Main Article Content
Abstract
Prostate cancer commonly metastasizes to bone due to its favorable microenvironment for cell growth and survival. Currently, the standard of care for metastatic prostate cancer is medical castration in conjunction with chemotherapeutic agents and newer anti-androgen/androgen receptor therapies. While these therapies aim to improve the quality of life in patients with advanced disease, resistance to these therapies is inevitable prompting the development of newer therapies to contain disease progression. The CXCL12/CXCR4 axis has previously been shown to be involved in prostate cancer cell homing to bone tissue, and new investigations found a novel interaction of Phosphatidyl Inositol 4 kinase IIIa (PI4KA) downstream of chemokine signaling. PI4KA phosphorylates at the 4th position on phosphatidylinositol (PI), to produce PI4P and is localized to the plasma membrane (PM). At the PM, PI4KA provides precursors for the generation of PI(4,5)P2, and PI(3,4,5)P3 and helps maintain PM identity through the recruitment of lipids and signaling proteins. PI4KA is recruited to the PM through evolutionarily conserved adaptor proteins, and in PC cells, CXCR4 binds with adaptor proteins to recruit PI4KA to the PM. The objective of this review is to summarize our understanding of the role that phosphatidyl inositol lipid messengers in cancer cells.
Article Details
How to Cite
RADOIU, Codrut et al.
A Novel Interaction between Chemokine and Phosphoinositide Signaling in Metastatic Prostate Cancer.
Medical Research Archives, [S.l.], v. 11, n. 7.1, july 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4020>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i7.1.4020.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Siegel DA, O'Neil ME, Richards TB, Dowling NF, Weir HK. Prostate Cancer Incidence and Survival, by Stage and Race/Ethnicity - United States, 2001-2017. MMWR Morb Mortal Wkly Rep. Oct 16 2020;69(41):1473-1480. doi:10.15585/mmwr.mm6941a1
2. Huang JF, Shen J, Li X, et al. Incidence of patients with bone metastases at diagnosis of solid tumors in adults: a large population-based study. Ann Transl Med. Apr 2020;8(7):482. doi:10.21037/atm.2020.03.55
3. Wong SK, Mohamad NV, Giaze TR, Chin KY, Mohamed N, Ima-Nirwana S. Prostate Cancer and Bone Metastases: The Underlying Mechanisms. Int J Mol Sci. May 27 2019;20(10)doi:10.3390/ijms20102587
4. Ban J, Fock V, Aryee DNT, Kovar H. Mechanisms, Diagnosis and Treatment of Bone Metastases. Cells. Oct 29 2021;10(11) doi:10.3390/cells10112944
5. Doehn C, Sommerauer M, Jocham D. Degarelix and its therapeutic potential in the treatment of prostate cancer. Clin Interv Aging. 2009;4:215-23. doi:10.2147/cia.s3503
6. Sayegh N, Swami U, Agarwal N. Recent Advances in the Management of Metastatic Prostate Cancer. JCO Oncol Pract. Jan 2022;18(1):45-55. doi:10.1200/OP.21.00206
7. Gravis G, Boher JM, Joly F, et al. Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial. Eur Urol. Aug 2016;70(2):256-62. doi:10.1016/j.eururo.2015.11.005
8. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. Aug 20 2015;373(8):737-46. doi:10.1056/NEJMoa1503747
9. Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. Jul 11 2019;381(2):121-131. doi:10.1056/NEJMoa1903835
10. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. Nov 10 2019;37(32):2974-2986. doi:10.1200/JCO.19.00799
11. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. Jul 27 2017;377(4):352-360. doi:10.1056/NEJMoa1704174
12. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. Jul 4 2019;381(1):13-24. doi:10.1056/NEJMoa1903307
13. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. May 26 2011;364(21):1995-2005. doi:10.1056/NEJMoa1014618
14. Body A, Pranavan G, Tan TH, Slobodian P. Medical management of metastatic prostate cancer. Aust Prescr. Oct 2018;41(5):154-159. doi:10.18773/austprescr.2018.046
15. Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet. Apr 30 2022;399(10336):1695-1707. doi:10.1016/S0140-6736(22)00367-1
16. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. Mar 24 2022;386(12):1132-1142. doi:10.1056/NEJMoa2119115
17. Knudsen KE, Penning TM. Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer. Trends Endocrinol Metab. May 2010;21(5):315-24. doi:10.1016/j.tem.2010.01.002
18. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. Jul 29 2010;363(5):411-22. doi:10.1056/NEJMoa1001294
19. Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. Mar 2020;23(1):38-52. doi:10.1038/s41391-019-0174-x
20. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. Sep 16 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
21. Hansen AR, Massard C, Ott PA, et al. Pembrolizumab for advanced prostate adenocarcinoma: findings of the KEYNOTE-028 study. Ann Oncol. Aug 1 2018;29(8):1807-1813. doi:10.1093/annonc/mdy232
22. Abida W, Campbell D, Patnaik A, et al. Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study. Clin Cancer Res. Jun 1 2020;26(11):2487-2496. doi:10.1158/1078-0432.CCR-20-0394
23. Hussain M, Mateo J, Fizazi K, et al. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. Dec 10 2020;383(24):2345-2357. doi:10.1056/NEJMoa2022485
24. Cai J, Kandagatla P, Singareddy R, et al. Androgens Induce Functional CXCR4 through ERG Factor Expression in TMPRSS2-ERG Fusion-Positive Prostate Cancer Cells. Transl Oncol. Jun 1 2010;3(3):195-203. doi:10.1593/tlo.09328
25. Singareddy R, Semaan L, Conley-Lacomb MK, et al. Transcriptional regulation of CXCR4 in prostate cancer: significance of TMPRSS2-ERG fusions. Mol Cancer Res. Nov 2013;11(11):1349-61. doi:10.1158/1541-7786.MCR-12-0705
26. Akashi T, Koizumi K, Tsuneyama K, Saiki I, Takano Y, Fuse H. Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer. Cancer Sci. Mar 2008;99(3):539-42. doi:10.1111/j.1349-7006.2007.00712.x
27. Jamaspishvili T, Berman DM, Ross AE, et al. Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol. Apr 2018;15(4):222-234. doi:10.1038/nrurol.2018.9
28. Conley-LaComb MK, Saliganan A, Kandagatla P, Chen YQ, Cher ML, Chinni SR. PTEN loss mediated Akt activation promotes prostate tumor growth and metastasis via CXCL12/CXCR4 signaling. Mol Cancer. Jul 31 2013;12(1):85. doi:10.1186/1476-4598-12-85
29. Chinni SR, Sivalogan S, Dong Z, et al. CXCL12/CXCR4 signaling activates Akt-1 and MMP-9 expression in prostate cancer cells: the role of bone microenvironment-associated CXCL12. Prostate. Jan 1 2006;66(1):32-48. doi:10.1002/pros.20318
30. Chinni SR, Yamamoto H, Dong Z, Sabbota A, Bonfil RD, Cher ML. CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and promotes growth of metastatic deposits in bone. Mol Cancer Res. Mar 2008;6(3):446-57. doi:10.1158/1541-7786.MCR-07-0117
31. Singh S, Singh UP, Grizzle WE, Lillard JW, Jr. CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion. Lab Invest. Dec 2004;84(12):1666-76. doi:10.1038/labinvest.3700181
32. Shiozawa Y, Pedersen EA, Havens AM, et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. Apr 2011;121(4):1298-312. doi:10.1172/JCI43414
33. Conley-LaComb MK, Semaan L, Singareddy R, et al. Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis. Mol Cancer. Nov 3 2016;15(1):68. doi:10.1186/s12943-016-0552-0
34. Sbrissa D, Semaan L, Govindarajan B, et al. A novel cross-talk between CXCR4 and PI4KIIIalpha in prostate cancer cells. Oncogene. Jan 2019;38(3):332-344. doi:10.1038/s41388-018-0448-0
35. Balla A, Balla T. Phosphatidylinositol 4-kinases: old enzymes with emerging functions. Trends Cell Biol. Jul 2006;16(7):351-61. doi:10.1016/j.tcb.2006.05.003
36. Di Paolo G, De Camilli P. Phosphoinositides in cell regulation and membrane dynamics. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review. Nature. Oct 12 2006;443(7112):651-7. doi:10.1038/nature05185
37. Pemberton JG, Kim YJ, Balla T. Integrated regulation of the phosphatidylinositol cycle and phosphoinositide-driven lipid transport at ER-PM contact sites. Traffic. Feb 2020;21(2):200-219. doi:10.1111/tra.12709
38. Sbrissa D, Ikonomov OC, Shisheva A. PIKfyve, a mammalian ortholog of yeast Fab1p lipid kinase, synthesizes 5-phosphoinositides. Effect of insulin. J Biol Chem. Jul 30 1999;274(31):21589-97. doi:10.1074/jbc.274.31.21589
39. Ikonomov OC, Sbrissa D, Delvecchio K, et al. The phosphoinositide kinase PIKfyve is vital in early embryonic development: preimplantation lethality of PIKfyve-/- embryos but normality of PIKfyve+/- mice. J Biol Chem. Apr 15 2011;286(15):13404-13. doi:10.1074/jbc.M111.222364
40. Baird D, Stefan C, Audhya A, Weys S, Emr SD. Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't. The Journal of cell biology. Dec 15 2008;183(6):1061-74. doi:10.1083/jcb.200804003
41. Baskin JM, Wu X, Christiano R, et al. The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane. Nat Cell Biol. Jan 2016;18(1):132-8. doi:10.1038/ncb3271
42. Nakatsu F, Baskin JM, Chung J, et al. PtdIns4P synthesis by PI4KIIIalpha at the plasma membrane and its impact on plasma membrane identity. J Cell Biol. Dec 10 2012;199(6):1003-16. doi:10.1083/jcb.201206095
43. Chung J, Nakatsu F, Baskin JM, De Camilli P. Plasticity of PI4KIIIalpha interactions at the plasma membrane. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't. EMBO reports. Mar 2015;16(3):312-20. doi:10.15252/embr.201439151
44. Adhikari H, Kattan WE, Kumar S, Zhou P, Hancock JF, Counter CM. Oncogenic KRAS is dependent upon an EFR3A-PI4KA signaling axis for potent tumorigenic activity. Nat Commun. Sep 9 2021;12(1):5248. doi:10.1038/s41467-021-25523-5
45. Balla A, Kim YJ, Varnai P, et al. Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylino-sitol 4-kinase IIIalpha. Mol Biol Cell. Feb 2008;19(2):711-21. doi:10.1091/mbc.e07-07-0713
46. Bojjireddy N, Botyanszki J, Hammond G, et al. Pharmacological and genetic targeting of the PI4KA enzyme reveals its important role in maintaining plasma membrane phosphatidy-linositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate levels. J Biol Chem. Feb 28 2014;289(9):6120-32. doi:10.1074/jbc.M113.531426
47. Myeong J, de la Cruz L, Jung SR, et al. Phosphatidylinositol 4,5-bisphosphate is regenerated by speeding of the PI 4-kinase pathway during long PLC activation. J Gen Physiol. Dec 7 2020;152(12) doi:10.1085/jgp.202012627
48. Gulyas G, Korzeniowski MK, Eugenio CEB, Vaca L, Kim YJ, Balla T. LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides. Cell Calcium. Sep 2022;106:102631. doi:10.1016/j.ceca.2022.102631
49. Waugh MG. The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer). Biochem J. Aug 28 2019;476(16):2321-2346. doi:10.1042/BCJ20180622
50. Chen C, Wang X, Xiong X, et al. Targeting type Igamma phosphatidylinositol phosphate kinase inhibits breast cancer metastasis. Oncogene. Aug 27 2015;34(35):4635-46. doi:10.1038/onc.2014.393
51. Choi S, Hedman AC, Sayedyahossein S, Thapa N, Sacks DB, Anderson RA. Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases. Nat Cell Biol. Dec 2016;18(12):1324-1335. doi:10.1038/ncb3441
52. Semenas J, Hedblom A, Miftakhova RR, et al. The role of PI3K/AKT-related PIP5K1alpha and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci U S A. Sep 2 2014;111(35):E3689-98. doi:10.1073/pnas.1405801111
53. Sun Y, Turbin DA, Ling K, et al. Type I gamma phosphatidylinositol phosphate kinase modulates invasion and proliferation and its expression correlates with poor prognosis in breast cancer. Breast Cancer Res. 2010;12(1):R6. doi:10.1186/bcr2471
54. Yamaguchi H, Yoshida S, Muroi E, et al. Phosphatidylinositol 4,5-bisphosphate and PIP5-kinase Ialpha are required for invadopodia formation in human breast cancer cells. Cancer Sci. Jul 2010;101(7):1632-8. doi:10.1111/j.1349-7006.2010.01574.x
55. Sechi AS, Wehland J. The actin cytoskeleton and plasma membrane connection: PtdIns(4,5)P(2) influences cytoskeletal protein activity at the plasma membrane. J Cell Sci. Nov 2000;113 Pt 21:3685-95. doi:10.1242/jcs.113.21.3685
2. Huang JF, Shen J, Li X, et al. Incidence of patients with bone metastases at diagnosis of solid tumors in adults: a large population-based study. Ann Transl Med. Apr 2020;8(7):482. doi:10.21037/atm.2020.03.55
3. Wong SK, Mohamad NV, Giaze TR, Chin KY, Mohamed N, Ima-Nirwana S. Prostate Cancer and Bone Metastases: The Underlying Mechanisms. Int J Mol Sci. May 27 2019;20(10)doi:10.3390/ijms20102587
4. Ban J, Fock V, Aryee DNT, Kovar H. Mechanisms, Diagnosis and Treatment of Bone Metastases. Cells. Oct 29 2021;10(11) doi:10.3390/cells10112944
5. Doehn C, Sommerauer M, Jocham D. Degarelix and its therapeutic potential in the treatment of prostate cancer. Clin Interv Aging. 2009;4:215-23. doi:10.2147/cia.s3503
6. Sayegh N, Swami U, Agarwal N. Recent Advances in the Management of Metastatic Prostate Cancer. JCO Oncol Pract. Jan 2022;18(1):45-55. doi:10.1200/OP.21.00206
7. Gravis G, Boher JM, Joly F, et al. Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial. Eur Urol. Aug 2016;70(2):256-62. doi:10.1016/j.eururo.2015.11.005
8. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. Aug 20 2015;373(8):737-46. doi:10.1056/NEJMoa1503747
9. Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. Jul 11 2019;381(2):121-131. doi:10.1056/NEJMoa1903835
10. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. Nov 10 2019;37(32):2974-2986. doi:10.1200/JCO.19.00799
11. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. Jul 27 2017;377(4):352-360. doi:10.1056/NEJMoa1704174
12. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. Jul 4 2019;381(1):13-24. doi:10.1056/NEJMoa1903307
13. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. May 26 2011;364(21):1995-2005. doi:10.1056/NEJMoa1014618
14. Body A, Pranavan G, Tan TH, Slobodian P. Medical management of metastatic prostate cancer. Aust Prescr. Oct 2018;41(5):154-159. doi:10.18773/austprescr.2018.046
15. Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet. Apr 30 2022;399(10336):1695-1707. doi:10.1016/S0140-6736(22)00367-1
16. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. Mar 24 2022;386(12):1132-1142. doi:10.1056/NEJMoa2119115
17. Knudsen KE, Penning TM. Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer. Trends Endocrinol Metab. May 2010;21(5):315-24. doi:10.1016/j.tem.2010.01.002
18. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. Jul 29 2010;363(5):411-22. doi:10.1056/NEJMoa1001294
19. Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. Mar 2020;23(1):38-52. doi:10.1038/s41391-019-0174-x
20. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. Sep 16 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
21. Hansen AR, Massard C, Ott PA, et al. Pembrolizumab for advanced prostate adenocarcinoma: findings of the KEYNOTE-028 study. Ann Oncol. Aug 1 2018;29(8):1807-1813. doi:10.1093/annonc/mdy232
22. Abida W, Campbell D, Patnaik A, et al. Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study. Clin Cancer Res. Jun 1 2020;26(11):2487-2496. doi:10.1158/1078-0432.CCR-20-0394
23. Hussain M, Mateo J, Fizazi K, et al. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. Dec 10 2020;383(24):2345-2357. doi:10.1056/NEJMoa2022485
24. Cai J, Kandagatla P, Singareddy R, et al. Androgens Induce Functional CXCR4 through ERG Factor Expression in TMPRSS2-ERG Fusion-Positive Prostate Cancer Cells. Transl Oncol. Jun 1 2010;3(3):195-203. doi:10.1593/tlo.09328
25. Singareddy R, Semaan L, Conley-Lacomb MK, et al. Transcriptional regulation of CXCR4 in prostate cancer: significance of TMPRSS2-ERG fusions. Mol Cancer Res. Nov 2013;11(11):1349-61. doi:10.1158/1541-7786.MCR-12-0705
26. Akashi T, Koizumi K, Tsuneyama K, Saiki I, Takano Y, Fuse H. Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer. Cancer Sci. Mar 2008;99(3):539-42. doi:10.1111/j.1349-7006.2007.00712.x
27. Jamaspishvili T, Berman DM, Ross AE, et al. Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol. Apr 2018;15(4):222-234. doi:10.1038/nrurol.2018.9
28. Conley-LaComb MK, Saliganan A, Kandagatla P, Chen YQ, Cher ML, Chinni SR. PTEN loss mediated Akt activation promotes prostate tumor growth and metastasis via CXCL12/CXCR4 signaling. Mol Cancer. Jul 31 2013;12(1):85. doi:10.1186/1476-4598-12-85
29. Chinni SR, Sivalogan S, Dong Z, et al. CXCL12/CXCR4 signaling activates Akt-1 and MMP-9 expression in prostate cancer cells: the role of bone microenvironment-associated CXCL12. Prostate. Jan 1 2006;66(1):32-48. doi:10.1002/pros.20318
30. Chinni SR, Yamamoto H, Dong Z, Sabbota A, Bonfil RD, Cher ML. CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and promotes growth of metastatic deposits in bone. Mol Cancer Res. Mar 2008;6(3):446-57. doi:10.1158/1541-7786.MCR-07-0117
31. Singh S, Singh UP, Grizzle WE, Lillard JW, Jr. CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion. Lab Invest. Dec 2004;84(12):1666-76. doi:10.1038/labinvest.3700181
32. Shiozawa Y, Pedersen EA, Havens AM, et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. Apr 2011;121(4):1298-312. doi:10.1172/JCI43414
33. Conley-LaComb MK, Semaan L, Singareddy R, et al. Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis. Mol Cancer. Nov 3 2016;15(1):68. doi:10.1186/s12943-016-0552-0
34. Sbrissa D, Semaan L, Govindarajan B, et al. A novel cross-talk between CXCR4 and PI4KIIIalpha in prostate cancer cells. Oncogene. Jan 2019;38(3):332-344. doi:10.1038/s41388-018-0448-0
35. Balla A, Balla T. Phosphatidylinositol 4-kinases: old enzymes with emerging functions. Trends Cell Biol. Jul 2006;16(7):351-61. doi:10.1016/j.tcb.2006.05.003
36. Di Paolo G, De Camilli P. Phosphoinositides in cell regulation and membrane dynamics. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review. Nature. Oct 12 2006;443(7112):651-7. doi:10.1038/nature05185
37. Pemberton JG, Kim YJ, Balla T. Integrated regulation of the phosphatidylinositol cycle and phosphoinositide-driven lipid transport at ER-PM contact sites. Traffic. Feb 2020;21(2):200-219. doi:10.1111/tra.12709
38. Sbrissa D, Ikonomov OC, Shisheva A. PIKfyve, a mammalian ortholog of yeast Fab1p lipid kinase, synthesizes 5-phosphoinositides. Effect of insulin. J Biol Chem. Jul 30 1999;274(31):21589-97. doi:10.1074/jbc.274.31.21589
39. Ikonomov OC, Sbrissa D, Delvecchio K, et al. The phosphoinositide kinase PIKfyve is vital in early embryonic development: preimplantation lethality of PIKfyve-/- embryos but normality of PIKfyve+/- mice. J Biol Chem. Apr 15 2011;286(15):13404-13. doi:10.1074/jbc.M111.222364
40. Baird D, Stefan C, Audhya A, Weys S, Emr SD. Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't. The Journal of cell biology. Dec 15 2008;183(6):1061-74. doi:10.1083/jcb.200804003
41. Baskin JM, Wu X, Christiano R, et al. The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane. Nat Cell Biol. Jan 2016;18(1):132-8. doi:10.1038/ncb3271
42. Nakatsu F, Baskin JM, Chung J, et al. PtdIns4P synthesis by PI4KIIIalpha at the plasma membrane and its impact on plasma membrane identity. J Cell Biol. Dec 10 2012;199(6):1003-16. doi:10.1083/jcb.201206095
43. Chung J, Nakatsu F, Baskin JM, De Camilli P. Plasticity of PI4KIIIalpha interactions at the plasma membrane. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't. EMBO reports. Mar 2015;16(3):312-20. doi:10.15252/embr.201439151
44. Adhikari H, Kattan WE, Kumar S, Zhou P, Hancock JF, Counter CM. Oncogenic KRAS is dependent upon an EFR3A-PI4KA signaling axis for potent tumorigenic activity. Nat Commun. Sep 9 2021;12(1):5248. doi:10.1038/s41467-021-25523-5
45. Balla A, Kim YJ, Varnai P, et al. Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylino-sitol 4-kinase IIIalpha. Mol Biol Cell. Feb 2008;19(2):711-21. doi:10.1091/mbc.e07-07-0713
46. Bojjireddy N, Botyanszki J, Hammond G, et al. Pharmacological and genetic targeting of the PI4KA enzyme reveals its important role in maintaining plasma membrane phosphatidy-linositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate levels. J Biol Chem. Feb 28 2014;289(9):6120-32. doi:10.1074/jbc.M113.531426
47. Myeong J, de la Cruz L, Jung SR, et al. Phosphatidylinositol 4,5-bisphosphate is regenerated by speeding of the PI 4-kinase pathway during long PLC activation. J Gen Physiol. Dec 7 2020;152(12) doi:10.1085/jgp.202012627
48. Gulyas G, Korzeniowski MK, Eugenio CEB, Vaca L, Kim YJ, Balla T. LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides. Cell Calcium. Sep 2022;106:102631. doi:10.1016/j.ceca.2022.102631
49. Waugh MG. The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer). Biochem J. Aug 28 2019;476(16):2321-2346. doi:10.1042/BCJ20180622
50. Chen C, Wang X, Xiong X, et al. Targeting type Igamma phosphatidylinositol phosphate kinase inhibits breast cancer metastasis. Oncogene. Aug 27 2015;34(35):4635-46. doi:10.1038/onc.2014.393
51. Choi S, Hedman AC, Sayedyahossein S, Thapa N, Sacks DB, Anderson RA. Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases. Nat Cell Biol. Dec 2016;18(12):1324-1335. doi:10.1038/ncb3441
52. Semenas J, Hedblom A, Miftakhova RR, et al. The role of PI3K/AKT-related PIP5K1alpha and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci U S A. Sep 2 2014;111(35):E3689-98. doi:10.1073/pnas.1405801111
53. Sun Y, Turbin DA, Ling K, et al. Type I gamma phosphatidylinositol phosphate kinase modulates invasion and proliferation and its expression correlates with poor prognosis in breast cancer. Breast Cancer Res. 2010;12(1):R6. doi:10.1186/bcr2471
54. Yamaguchi H, Yoshida S, Muroi E, et al. Phosphatidylinositol 4,5-bisphosphate and PIP5-kinase Ialpha are required for invadopodia formation in human breast cancer cells. Cancer Sci. Jul 2010;101(7):1632-8. doi:10.1111/j.1349-7006.2010.01574.x
55. Sechi AS, Wehland J. The actin cytoskeleton and plasma membrane connection: PtdIns(4,5)P(2) influences cytoskeletal protein activity at the plasma membrane. J Cell Sci. Nov 2000;113 Pt 21:3685-95. doi:10.1242/jcs.113.21.3685