|Table of Contents|

Advances in biological functions of DKK1 protein in tumor development and related therapeutic strategies

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 21
Page:
4173-4177
Research Field:
Publishing date:

Info

Title:
Advances in biological functions of DKK1 protein in tumor development and related therapeutic strategies
Author(s):
HU BowenXU CongWANG XinWEN ShaodiSHEN Bo
The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research,Jiangsu Nanjing 210000,China.
Keywords:
Dickkop-1cancerimmunotherapyDKN-01
PACS:
R730
DOI:
10.3969/j.issn.1672-4992.2024.21.029
Abstract:
Dickkop-1,a secreted protein,is highly expressed in a variety of solid tumors and hematological tumors,and DKK1 can predict the prognosis of most tumor patients.Many studies have shown that DKK1 not only directly affects the biological behavior of tumor cell proliferation and angiogenesis,but also affects the efficacy of tumor immunotherapy by inducing immunosuppressive tumor microenvironment.Neutralization of DKK1 signal can not only reverse the tumor inhibitory immune microenvironment,but also have a certain symptomatic remission effect on distant tumor metastases such as brain metastasis and bone metastasis.DKK1 antibody has been widely used in preclinical and clinical studies of a variety of tumors,providing a new therapeutic strategy for the comprehensive treatment of tumors.

References:

[1]GLINKA A,WU W,DELIUS H,et al.Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction[J].Nature,1998,391(6665):357-362.
[2] PINZONE JJ,HALL BM,THUDI NK,et al.The role of Dickkopf-1 in bone development,homeostasis,and disease[J].Blood,2009,113(3):517-525.
[3] HUANG Y,LIU L,LIU A.Dickkopf-1:Current knowledge and related diseases[J].Life Sci,2018,209:249-254.
[4] D'AMICO L,MAHAJAN S,CAPIETTO AH,et al.Dickkopf-related protein 1(Dkk1) regulates the accumulation and function of myeloid derived suppressor cells in cancer[J].J Exp Med,2016,213(5):827-840.
[5] PARSONS MJ,TAMMELA T,DOW LE.WNT as a driver and dependency in cancer[J].Cancer Discov,2021,11(10):2413-2429.
[6] KIKUCHI A,MATSUMOTO S,SADA R.Dickkopf signaling,beyond Wnt-mediated biology[J].Semin Cell Dev Biol,2022,125:55-65.
[7] IGUCHI K,SADA R,MATSUMOTO S,et al.DKK1-CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness[J].Cancer Sci,2023,114(5):2063-2077.
[8] YAO L,ZHANG D,ZHAO X,et al.Dickkopf-1-promoted vasculogenic mimicry in non-small cell lung cancer is associated with EMT and development of a cancer stem-like cell phenotype[J].J Cell Mol Med,2016,20(9):1673-1685.
[9] QIAO R,ZHONG R,CHANG Q,et al.Serum dickkopf-1 as a clinical and prognostic factor in non-small cell lung cancer patients with bone metastases[J].Oncotarget,2017,8(45):79469-79479.
[10] KASOHA M,BOHLE RM,SEIBOLD A,et al.Dickkopf-1(Dkk1) protein expression in breast cancer with special reference to bone metastases[J].Clin Exp Metastasis,2018,35(8):763-775.
[11] KASOHA M,STEINBACH AK,BOHLE RM,et al.Dkk1 as a prognostic marker for neoadjuvant chemotherapy response in breast cancer patients[J].Cancers(Basel),2024,16(2):419.
[12] ZHAO C,LIU L,HE Q,et al.Dickkopf-1 is an immune infiltration-related prognostic biomarker of head and neck squamous cell carcinoma[J].Aging(Albany NY),2024,16(4):3837-3855.
[13] FENG Y,ZHANG Y,WEI X,et al.Correlations of DKK1 with pathogenesis and prognosis of human multiple myeloma[J].Cancer Biomark,2019,24(2):195-201.
[14] CAO M,WANG Y,LU G,et al.Classical angiogenic signaling pathways and novel anti-angiogenic strategies for colorectal cancer[J].Curr Issues Mol Biol,2022,44(10):4447-4471.
[15] WISE DR,SCHNEIDER JA,ARMENIA J,et al.Dickkopf-1 can lead to immune evasion in metastatic castration-resistant prostate cancer[J].JCO Precis Oncol,2020,4:PO.20.00097.
[16] SHI T,ZHANG Y,WANG Y,et al.DKK1 promotes tumor immune evasion and impedes anti-PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer[J].Cancer Immunol Res,2022,10(12):1506-1524.
[17] LI J,ZHANG Y,YE F,et al.DKK1 promotes epithelial-mesenchymal transition and cisplatin resistance in gastric cancer via activation of the PI3K/AKT pathway[J].Cancers(Basel),2023,15(19):4756.
[18] SUI Q,LIU D,JIANG W,et al.Dickkopf 1 impairs the tumor response to PD-1 blockade by inactivating CD8+ T cells in deficient mismatch repair colorectal cancer[J].J Immunother Cancer,2021,9(3):e001498.
[19] YE X,LIU J,QUAN R,et al.DKK1 affects survival of patients with head and neck squamous cell carcinoma by inducing resistance to radiotherapy and immunotherapy[J].Radiother Oncol,2023,181:109485.
[20] YANG RH,QIN J,CAO JL,et al.Dickkopf-1 drives tumor immune evasion by inducing PD-L1 expression in hepatocellular carcinoma[J].Biochem Pharmacol,2023,208:115378.
[21] WU M,ZHANG X,ZHANG W,et al.Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis[J].Nat Commun,2022,13(1):1371.
[22] MOON SJ,CHOI HJ,KYE YH,et al.CTTN overexpression confers cancer stem cell-like properties and trastuzumab resistance via DKK-1/WNT signaling in HER2 positive breast cancer[J].Cancers(Basel),2023,15(4):1168.
[23] ZHUANG X,ZHANG H,LI X,et al.Differential effects on lung and bone metastasis of breast cancer by Wnt signalling inhibitor DKK1[J].Nat Cell Biol,2017,19(10):1274-1285.
[24] YUAN S,HOGGARD NK,KANTAKE N,et al.Effects of Dickkopf-1(DKK-1) on prostate cancer growth and bone metastasis[J].Cells,2023,12(23):2695.
[25] XU Y,HU J,LYU Q,et al.Endometrium-derived mesenchymal stem cells suppress progression of endometrial cancer via the DKK1-Wnt/β-catenin signaling pathway[J].Stem Cell Res Ther,2023,14(1):159.
[26]ZHOU HJ,ZHOU M.The diagnostic value of serum DKK1 in endometrial cancer[J].Modern Oncology,2018,25(20):3293-3296.
[27] GAN DX,WANG YB,HE MY,et al.Lung cancer cells-controlled Dkk-1 production in brain metastatic cascade drive microglia to acquire a pro-tumorigenic phenotype[J].Front Cell Dev Biol,2020,8:591405.
[28] LI X,WANG J,ZHU S,et al.DKK1 activates noncanonical NF-κB signaling via IL-6-induced CKAP4 receptor in multiple myeloma[J].Blood Adv,2021,5(18):3656-3667.
[29] GIRALT I,GALLO-OLLER G,NAVARRO N,et al.Dickkopf-1 inhibition reactivates Wnt/β-Catenin signaling in rhabdomyosarcoma,induces myogenic markers in vitro and impairs tumor cell survival in vivo[J].Int J Mol Sci,2021,22(23):12921.
[30] DI M,ZHANG Y,ZENG R,et al.The pro-angiogenesis effect of miR33a-5p/Ets-1/DKK1 signaling in ox-LDL induced HUVECs[J].Int J Biol Sci,2021,17(15):4122-4139.
[31] WANG Y,YU H,XIE X,et al.Plasmalemma vesicle-associated protein promotes angiogenesis in cholangiocarcinoma via the DKK1/CKAP4/PI3K signaling pathway[J].Oncogene,2021,40(25):4324-4337.
[32] ZHAI J,CHEN H,WONG CC,et al.ALKBH5 drives immune suppression via targeting AXIN2 to promote colorectal cancer and is a target for boosting immunotherapy[J].Gastroenterology,2023,165(2):445-462.
[33] ZHANG Y,LIANG K,ZHOU X,et al.Combination therapy of DKK1 inhibition and NKG2D chimeric antigen receptor T cells for the treatment of gastric cancer[J].Cancer Sci,2023,114(7):2798-2809.
[34] SIMIC MK,MOHANTY ST,XIAO Y,et al.Multi-targeting DKK1 and LRP6 prevents bone loss and improves fracture resistance in multiple myeloma[J].J Bone Miner Res,2023,38(6):814-828.
[35] NAGOYA A,SADA R,KIMURA H,et al.CKAP4 is a potential exosomal biomarker and therapeutic target for lung cancer[J].Transl Lung Cancer Res,2023,12(3):408-426.
[36] HAAS MS,KAGEY MH,HEATH H,et al.mDKN-01,a novel Anti-DKK1 mAb,enhances innate immune responses in the tumor microenvironment[J].Mol Cancer Res,2021,19(4):717-725.
[37] BETELLA I,TURBITT W J,SZUL T,et al.Dkn-01:A promising strategy for targeting the Wnt pathway in ovarian cancer[J].Gynecologic Oncology,2019,154:55.
[38] JARMAN EJ,HORCAS-LOPEZ M,WADDELL SH,et al.DKK1 drives immune suppressive phenotypes in intrahepatic cholangiocarcinoma and can be targeted with anti-DKK1 therapeutic DKN-01[J].Liver Int,2023,43(1):208-220.
[39] AREND R,DHOLAKIA J,CASTRO C,et al.DKK1 is a predictive biomarker for response to DKN-01:Results of a phase 2 basket study in women with recurrent endometrial carcinoma[J].Gynecol Oncol,2023,172:82-91.
[40] KLEMPNER SJ,BENDELL JC,VILLAFLOR VM,et al.Safety,efficacy,and biomarker results from a phase Ib study of the anti-DKK1 antibody DKN-01 in combination with pembrolizumab in advanced esophagogastric cancers[J].Mol Cancer Ther,2021,20(11):2240-2249.
[41] QIAN J,WANG Q,XIAO L,et al.Development of therapeutic monoclonal antibodies against DKK1 peptide-HLA-A2 complex to treat human cancers[J].J Immunother Cancer,2024,12(1):e008145.

Memo

Memo:
National Natural Science Foundation of China(No.82272863);国家自然科学基金资助项目(编号:82272863);吴阶平医学基金会临床科研专项基金(编号:320.6750.2022-22-61)
Last Update: 2024-09-30