A Tumor Suppressor Function for the Lipid Phosphatase INPP4B in Melanocytic Neoplasms

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2013 Nov 30

PMID 24288008

Citations 26

Authors

Rolando Perez-Lorenzo

Kamraan Z Gill

Che-Hung Shen

Feng X Zhao

Bin Zheng

Hans-Joachim Schulze

David N Silvers

Georg Brunner

Basil A Horst

Affiliations

Soon will be listed here.

Abstract

The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.

Citing Articles

The Transcriptional Landscape of Immune-Response 3'-UTR Alternative Polyadenylation in Melanoma.

Yang X, Wu Y, Chen X, Qiu J, Huang C Int J Mol Sci. 2024; 25(5).

PMID: 38474285 PMC: 10931711. DOI: 10.3390/ijms25053041.

Role of INPP4B in the proliferation, migration, invasion, and survival of human endometrial cancer cells.

Zhao J, Du X, Si W, Zhao X, Zhou Z Histol Histopathol. 2024; 39(9):1197-1208.

PMID: 38318760 DOI: 10.14670/HH-18-711.

Genes regulated by DNA methylation are involved in distinct phenotypes during melanoma progression and are prognostic factors for patients.

Papaiz D, Rius F, Ayub A, Origassa C, Gujar H, De Oliveira Pessoa D Mol Oncol. 2022; 16(9):1913-1930.

PMID: 35075772 PMC: 9067153. DOI: 10.1002/1878-0261.13185.

INPP4B exerts a dual role in gastric cancer progression and prognosis.

Wu Y, Wang X, Lu Y, Wang H, Wang M, You Y J Cancer. 2021; 12(23):7201-7213.

PMID: 34729121 PMC: 8558642. DOI: 10.7150/jca.58397.

INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer.

Rodgers S, Ooms L, Oorschot V, Schittenhelm R, Nguyen E, Hamila S Nat Commun. 2021; 12(1):3140.

PMID: 34035258 PMC: 8149851. DOI: 10.1038/s41467-021-23241-6.

References

Tsao H, Goel V, Wu H, Yang G, Haluska F . Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J Invest Dermatol. 2004; 122(2):337-41. PMC: 2586668. DOI: 10.1046/j.0022-202X.2004.22243.x. View

Kudchadkar R, Smalley K, Glass L, Trimble J, Sondak V . Targeted therapy in melanoma. Clin Dermatol. 2013; 31(2):200-8. DOI: 10.1016/j.clindermatol.2012.08.013. View

Engelman J . Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009; 9(8):550-62. DOI: 10.1038/nrc2664. View

Westbrook T, Martin E, Schlabach M, Leng Y, Liang A, Feng B . A genetic screen for candidate tumor suppressors identifies REST. Cell. 2005; 121(6):837-48. DOI: 10.1016/j.cell.2005.03.033. View

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2012. CA Cancer J Clin. 2012; 62(1):10-29. DOI: 10.3322/caac.20138. View

Cantley L . The phosphoinositide 3-kinase pathway. Science. 2002; 296(5573):1655-7. DOI: 10.1126/science.296.5573.1655. View

Madhunapantula S, Robertson G . The PTEN-AKT3 signaling cascade as a therapeutic target in melanoma. Pigment Cell Melanoma Res. 2009; 22(4):400-19. PMC: 3610526. DOI: 10.1111/j.1755-148X.2009.00585.x. View

Lin W, Baker A, Beroukhim R, Winckler W, Feng W, Marmion J . Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res. 2008; 68(3):664-73. PMC: 10493008. DOI: 10.1158/0008-5472.CAN-07-2615. View

Tsao H, Zhang X, Fowlkes K, Haluska F . Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines. Cancer Res. 2000; 60(7):1800-4. View

10.

Norris F, Atkins R, MAJERUS P . The cDNA cloning and characterization of inositol polyphosphate 4-phosphatase type II. Evidence for conserved alternative splicing in the 4-phosphatase family. J Biol Chem. 1997; 272(38):23859-64. DOI: 10.1074/jbc.272.38.23859. View

11.

Nikolaou V, Stratigos A, Flaherty K, Tsao H . Melanoma: new insights and new therapies. J Invest Dermatol. 2012; 132(3 Pt 2):854-63. PMC: 3759013. DOI: 10.1038/jid.2011.421. View

12.

Norris F, Auethavekiat V, MAJERUS P . The isolation and characterization of cDNA encoding human and rat brain inositol polyphosphate 4-phosphatase. J Biol Chem. 1995; 270(27):16128-33. DOI: 10.1074/jbc.270.27.16128. View

13.

Ferron M, Vacher J . Characterization of the murine Inpp4b gene and identification of a novel isoform. Gene. 2006; 376(1):152-61. DOI: 10.1016/j.gene.2006.02.022. View

14.

Sarbassov D, Guertin D, Ali S, Sabatini D . Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005; 307(5712):1098-101. DOI: 10.1126/science.1106148. View

15.

Ye Y, Jin L, Wilmott J, Hu W, Yosufi B, Thorne R . PI(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma. Nat Commun. 2013; 4:1508. PMC: 3586716. DOI: 10.1038/ncomms2489. View

16.

Dankort D, Curley D, Cartlidge R, Nelson B, Karnezis A, Damsky Jr W . Braf(V600E) cooperates with Pten loss to induce metastatic melanoma. Nat Genet. 2009; 41(5):544-52. PMC: 2705918. DOI: 10.1038/ng.356. View

17.

Gewinner C, Wang Z, Richardson A, Teruya-Feldstein J, Etemadmoghadam D, Bowtell D . Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell. 2009; 16(2):115-25. PMC: 2957372. DOI: 10.1016/j.ccr.2009.06.006. View

18.

Ross M, Zhou X, Song G, Shurtleff S, Girtman K, Williams W . Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood. 2003; 102(8):2951-9. DOI: 10.1182/blood-2003-01-0338. View

19.

Clement S, Krause U, Desmedt F, Tanti J, Behrends J, Pesesse X . The lipid phosphatase SHIP2 controls insulin sensitivity. Nature. 2001; 409(6816):92-7. DOI: 10.1038/35051094. View

20.

Dull T, Zufferey R, Kelly M, Mandel R, Nguyen M, Trono D . A third-generation lentivirus vector with a conditional packaging system. J Virol. 1998; 72(11):8463-71. PMC: 110254. DOI: 10.1128/JVI.72.11.8463-8471.1998. View