Metastatic latency and immune evasion through autocrine inhibition of WNT Journal Article


Authors: Malladi, S.; Macalinao, D. G.; Jin, X.; He, L.; Basnet, H.; Zou, Y.; De Stanchina, E.; Massagué, J.
Article Title: Metastatic latency and immune evasion through autocrine inhibition of WNT
Abstract: Metastasis frequently develops years after the removal of a primary tumor, from a minority of disseminated cancer cells that survived as latent entities through unknown mechanisms. We isolated latency competent cancer (LCC) cells from early stage human lung and breast carcinoma cell lines and defined the mechanisms that suppress outgrowth, support long-term survival, and maintain tumor-initiating potential in these cells during the latent metastasis stage. LCC cells show stem-cell-like characteristics and express SOX2 and SOX9 transcription factors, which are essential for their survival in host organs under immune surveillance and for metastatic outgrowth under permissive conditions. Through expression of the WNT inhibitor DKK1, LCC cells self-impose a slow-cycling state with broad downregulation of ULBP ligands for NK cells and evasion of NK-cell-mediated clearance. By expressing a Sox-dependent stem-like state and actively silencing WNT signaling, LCC cells can enter quiescence and evade innate immunity to remain latent for extended periods. © 2016 Elsevier Inc.
Journal Title: Cell
Volume: 165
Issue: 1
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2016-03-24
Start Page: 45
End Page: 60
Language: English
DOI: 10.1016/j.cell.2016.02.025
PROVIDER: scopus
PMCID: PMC4808520
PUBMED: 27015306
DOI/URL:
Notes: Article -- Export Date: 2 May 2016 -- Source: Scopus
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MSK Authors
  1. Joan Massague
    276 Massague
  2. Yilong Zou
    13 Zou
  3. Xin Jin
    5 Jin
  4. Lan   He
    1 He
  5. Harihar   Basnet
    1 Basnet