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Dickkopf1: A tumor suppressor or metastasis promoter?
Author(s) -
Menezes Mitchell E.,
Devine Daniel J.,
Shevde Lalita A.,
Samant Rajeev S.
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26449
Subject(s) - dkk1 , wnt signaling pathway , suppressor , downregulation and upregulation , regulator , prostate cancer , cancer research , metastasis , tumor progression , tumor microenvironment , cancer , catenin , biology , medicine , tumor cells , microbiology and biotechnology , signal transduction , genetics , gene
Dickkopf1 (DKK1), a secreted inhibitor of the Wnt/β‐catenin pathway, is a negative regulator of bone formation. DKK1 acts as a switch that transitions prostate cancer bone metastases from osteolytic to osteoblastic and also is an active indicator of poor outcome for multiple myeloma. However, in other tumor types, DKK1 upregulation or overexpression suppresses tumor growth. Thus, the role of DKK1 in cancer appears to be diverse. This raises a question: Could the increased levels of DKK1 still be tumor protective when observed in high levels in the serum of patients? Here, we summarize the diverse, seemingly contradicting roles of DKK1 and attempt to explain the apparent dichotomy in its activity. We propose that DKK1 is a critical secreted factor that modulates microenvironment. Based on the location and components of the microenvironment DKK1 will support different outcomes.