Background
Micropapillary-predominant adenocarcinoma (MPA) of the lung is associated with extensive lymph node involvement and rapid terminal metastasis. However, this subtype has been recognized for only a few years, and there have been few studies of the molecular mechanisms associated with its highly invasive behaviors.
Conclusions
Our data support the need for further research regarding the WNT/β-catenin pathway and the need to develop novel targeted therapies for restoration of tumor cell adherence and improvement of the prognosis of MPA.
Methods
The present study utilized immunohistochemical staining of surgically resected tissue blocks of MPA and lepidic-predominant lung adenocarcinoma to quantify the expression of specific biological markers in the WNT/β-catenin pathway and evaluate their influence on the lymph nodes invasion of these two types of lung adenocarcinomas.
Results
Our findings revealed that disruption of the cell membrane cadherin-catenin complex, which weakens the tumor cell adherence of MPA, was caused by the dissociation of β-catenin from the cadherin-catenin complex and the subsequent accumulation of β-catenin in the cytoplasm. This caused abnormal activation of the WNT/β-catenin pathway. We also found that Wnt-1-specific overexpression and Axin1 inhibition in MPA could explain the redistribution and cytoplasmic retention of β-catenin. Collectively, these findings suggest that an abnormality in the WNT/β-catenin pathway could enhance the invasiveness of MPA through the overexpression of Wnt-1 and downregulation of Axin1 molecules. Conclusions: Our data support the need for further research regarding the WNT/β-catenin pathway and the need to develop novel targeted therapies for restoration of tumor cell adherence and improvement of the prognosis of MPA.