Dickkopf1: a tumor suppressor or metastasis promoter?

Abstract:

: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.

journal_name

Int J Cancer

authors

Menezes ME,Devine DJ,Shevde LA,Samant RS

doi

10.1002/ijc.26449

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

1477-83

issue

7

eissn

0020-7136

issn

1097-0215

journal_volume

130

pub_type

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