Factors affecting the role of canonical Wnt inhibitor Dickkopf-1 in cancer progression

Frontiers in Oncology

Oncology

Carl A. Gregory¹  Connor Brubaker²  Donald Turner²  Dakota Doucet³ 

[1] Department of Cell Biology and Genetics, Texas A&M Health Science Center School of Medicine, Texas A&M University, Bryan, TX, United States;Department of Statistics, Texas A&M University, College Station, TX, United States;Medical Sciences Program, Texas A&M Health Science Center School of Medicine, Texas A&M University, Bryan, TX, United States;

关键词: Dickkopf (DKK);    Wnt signaling;    stroma;    cancer;    immunomodulation;    angiogenesis;    survival;    chemoresistance;   

DOI  :  10.3389/fonc.2023.1114822

 received in 2022-12-02, accepted in 2023-03-01,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe canonical Wnt inhibitor Dickkopf-1 (Dkk-1) has the capacity to modulate homeostasis between canonical and non-canonical Wnt pathways and also signal independently of Wnt. The specific effects of Dkk-1 activity on tumor physiology are therefore unpredictable with examples of Dkk-1 serving as either a driver or suppressor of malignancy. Given that Dkk-1 blockade may serve as a potential treatment for some types of cancer, we questioned whether it is possible to predict the role of Dkk-1 on tumor progression based on the tissue origin of the tumor.MethodsOriginal research articles that described Dkk-1 in terms a tumor suppressor or driver of cancer growth were identified. To determine the association between tumor developmental origin and the role of Dkk-1, a logistic regression was performed. The Cancer Genome Atlas database was interrogated for survival statistics based on tumor Dkk-1 expression.ResultsWe report that Dkk-1 is statistically more likely to serve as a suppressor in tumors arising from the ectoderm (p = 0.0198) or endoderm (p = 0.0334) but more likely to serve as a disease driver in tumors of mesodermal origin (p = 0.0155). Survival analyses indicated that in cases where Dkk-1 expression could be stratified, high Dkk-1 expression is usually associated with poor prognosis. This in part may be due to pro-tumorigenic role Dkk-1 plays on tumor cells but also through its influence on immunomodulatory and angiogenic processes in the tumor stroma.ConclusionDkk-1 has a context-specific dual role as a tumor suppressor or driver. Dkk-1 is significantly more likely to serve as a tumor suppressor in tumors arising from ectoderm and endoderm while the converse is true for mesodermal tumors. Patient survival data indicated high Dkk-1 expression is generally a poor prognostic indicator. These findings provide further support for the importance of Dkk-1 as a therapeutic cancer target in some cases.

【 授权许可】

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Copyright © 2023 Doucet, Brubaker, Turner and Gregory