Tumour YAP1 and PTEN Expression Correlates with Tumour-associated Myeloid Suppressor Cell Expansion and Reduced Survival in Colorectal Cancer

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2018 May 18

PMID 29770434

Citations 25

Authors

Rong Yang

Ting-Ting Cai

Xiao-Jun Wu

Yi-Na Liu

Jia He

Xiao-Shi Zhang

Gang Ma

Jiang Li

Affiliations

Soon will be listed here.

Abstract

The expansion of myeloid-derived suppressor cells (MDSCs) correlates with tumorigenesis in colorectal cancer (CRC). Here, we found a significant association between CD33 MDSC number and Yes-associated protein 1 (YAP1) and phosphatase and tensin homologue (PTEN) levels in CRC patients (P < 0·05). Moreover, the CD33 MDSCs, YAP1 and PTEN were identified as predictors for the prognosis of CRC patients (P < 0·05). Notably, CD33 MDSCs were an independent survival predictor for CRC patients through a Cox model analysis. In vitro data determined that the expression levels of YAP1 and PTEN in CRC-derived cell lines were associated with CRC-derived MDSC induction, and the blockade of YAP1 and PTEN decreased CRC-derived MDSC induction. A mechanistic analysis revealed that YAP1 promoted CRC-derived MDSC induction by suppressing PTEN expression to up-regulate COX-2, P-AKT and P-p65 in CRC-derived cells, leading to secretion of the cytokine granulocyte-macrophage colony-stimulating factor. Our findings establish a novel mechanism of pro-tumorigenic MDSC induction mediated by ectopic YAP1 and PTEN expression in CRC.

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References

Chen W, Zheng R, Zeng H, Zhang S . The incidence and mortality of major cancers in China, 2012. Chin J Cancer. 2016; 35(1):73. PMC: 4971631. DOI: 10.1186/s40880-016-0137-8. View

Konsavage Jr W, Kyler S, Rennoll S, Jin G, Yochum G . Wnt/β-catenin signaling regulates Yes-associated protein (YAP) gene expression in colorectal carcinoma cells. J Biol Chem. 2012; 287(15):11730-9. PMC: 3320921. DOI: 10.1074/jbc.M111.327767. View

Atefi M, Avramis E, Lassen A, Wong D, Robert L, Foulad D . Effects of MAPK and PI3K pathways on PD-L1 expression in melanoma. Clin Cancer Res. 2014; 20(13):3446-57. PMC: 4079734. DOI: 10.1158/1078-0432.CCR-13-2797. View

Marvel D, Gabrilovich D . Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest. 2015; 125(9):3356-64. PMC: 4588239. DOI: 10.1172/JCI80005. View

Tumaneng K, Schlegelmilch K, Russell R, Yimlamai D, Basnet H, Mahadevan N . YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29. Nat Cell Biol. 2012; 14(12):1322-9. PMC: 4019071. DOI: 10.1038/ncb2615. View

Peng W, Chen J, Liu C, Malu S, Creasy C, Tetzlaff M . Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy. Cancer Discov. 2015; 6(2):202-16. PMC: 4744499. DOI: 10.1158/2159-8290.CD-15-0283. View

Zhang H, Ramakrishnan S, Triner D, Centofanti B, Maitra D, Gyorffy B . Tumor-selective proteotoxicity of verteporfin inhibits colon cancer progression independently of YAP1. Sci Signal. 2015; 8(397):ra98. PMC: 4818013. DOI: 10.1126/scisignal.aac5418. View

Wang G, Lu X, Dey P, Deng P, Wu C, Jiang S . Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression. Cancer Discov. 2015; 6(1):80-95. PMC: 4707102. DOI: 10.1158/2159-8290.CD-15-0224. View

Zhang Q, Zhang L, Li L, Wang Z, Ying J, Fan Y . Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis. Cancer Lett. 2014; 354(2):227-34. DOI: 10.1016/j.canlet.2014.07.040. View

10.

Liang K, Zhou G, Zhang Q, Li J, Zhang C . Expression of hippo pathway in colorectal cancer. Saudi J Gastroenterol. 2014; 20(3):188-94. PMC: 4067916. DOI: 10.4103/1319-3767.133025. View

11.

Chun E, Lavoie S, Michaud M, Gallini C, Kim J, Soucy G . CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function. Cell Rep. 2015; 12(2):244-57. PMC: 4620029. DOI: 10.1016/j.celrep.2015.06.024. View

12.

Moreno B, Zaretsky J, Garcia-Diaz A, Tsoi J, Parisi G, Robert L . Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells. Cancer Immunol Res. 2016; 4(10):845-857. PMC: 5050168. DOI: 10.1158/2326-6066.CIR-16-0060. View

13.

Pietrzyk L . Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates. Dis Markers. 2016; 2016:4912405. PMC: 5124654. DOI: 10.1155/2016/4912405. View

14.

Alizadeh D, Larmonier N . Chemotherapeutic targeting of cancer-induced immunosuppressive cells. Cancer Res. 2014; 74(10):2663-8. PMC: 4041515. DOI: 10.1158/0008-5472.CAN-14-0301. View

15.

Lugli A, Karamitopoulou E, Zlobec I . Tumour budding: a promising parameter in colorectal cancer. Br J Cancer. 2012; 106(11):1713-7. PMC: 3364122. DOI: 10.1038/bjc.2012.127. View

16.

Liu Y, Lai L, Chen Q, Song Y, Xu S, Ma F . MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J Immunol. 2012; 188(11):5500-10. DOI: 10.4049/jimmunol.1103505. View

17.

McCarthy N . Signalling: YAP, PTEN and miR-29 size each other up. Nat Rev Cancer. 2012; 13(1):4-5. DOI: 10.1038/nrc3422. View

18.

Gajewski T, Schreiber H, Fu Y . Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013; 14(10):1014-22. PMC: 4118725. DOI: 10.1038/ni.2703. View

19.

OuYang L, Wu X, Ye S, Zhang R, Li Z, Liao W . Tumor-induced myeloid-derived suppressor cells promote tumor progression through oxidative metabolism in human colorectal cancer. J Transl Med. 2015; 13:47. PMC: 4357065. DOI: 10.1186/s12967-015-0410-7. View

20.

Ghiringhelli F, Apetoh L, Housseau F, Kroemer G, Zitvogel L . Links between innate and cognate tumor immunity. Curr Opin Immunol. 2007; 19(2):224-31. DOI: 10.1016/j.coi.2007.02.003. View