E-cadherin loss accelerates tumor progression and metastasis in a mouse model of lung adenocarcinoma

Kerstin W. Sinkevicius, Kelly J. Bellaria, Juliana Barrios, Patrizia Pessina, Manav Gupta, Christine Fillmore Brainson, Roderick T. Bronson, Carla F. Kim

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Metastatic disease is the primary cause of death of patients with lung cancer, but the mouse models of lung adenocarcinoma do not accurately recapitulate the tumor microenvironment or metastatic disease observed in patients. In this study, we conditionally deleted E-cadherin in an autochthonous lung adenocarcinoma mouse model driven by activated oncogenic Kras and p53 loss. Loss of E-cadherin significantly accelerated lung adenocarcinoma progression and decreased survival of the mice. Kras;p53;E-cadherin mice had a 41% lung tumor burden, invasive grade 4 tumors, and a desmoplastic stroma just 8 weeks after tumor initiation. One hundred percent of the mice developed local metastases to the lymph nodes or chest wall, and 38% developed distant metastases to the liver or kidney. Lung adenocarcinoma cancer cell lines derived from these tumors also had high migratory rates. These studies demonstrate that the Kras;p53;E-cadherin mouse model better emulates the tumor microenvironment and metastases observed in patients with lung adenocarcinoma than previous models and may therefore be useful for studying metastasis and testing new lung cancer treatments in vivo.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number2
StatePublished - Aug 2018

Bibliographical note

Funding Information:
Supported by American Cancer Society Postdoctoral Fellowship PF-09-121-01-DDC, a Harvard Stem Cell Institute National Institutes of Health (NIH) training grant, the Free to Breathe (formerly the National Lung Cancer Partnership) 2012 Young Investigator Research Grant (K.W.S.). Support was also provided by the V Foundation for Cancer Research; American Cancer Society Research Scholar grant RSG-08-082-01-MGO; the Freeman Trust; the Harvard Stem Cell Institute; NIH/National Heart, Lung, and Blood Institute grants R01 HL090136, R01 HL132266, R01 HL125821, U01 HL100402, and RFA-HL-09-004; the Thoracic Foundation; the Ellison Foundation; Joan’s Legacy; and the Boston Children’s Hospital Faculty Career Development Fellowship (C.F.K.).

Funding Information:
The authors thank members of the Kim laboratory for critical reading of the manuscript and helpful discussions.

Publisher Copyright:
Copyright © 2018 by the American Thoracic Society.


  • E-cadherin
  • Kras
  • Metastasis
  • Non–small cell lung cancer
  • P53

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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