Activation of KRAS promotes the mesenchymal features of basal-type breast cancer

Basal-type breast cancers are among the most aggressive and deadly breast cancer subtypes, displaying a high metastatic ability associated with mesenchymal features. However, the molecular mechanisms underlying the maintenance of mesenchymal phenotypes of basal-type breast cancer cells remain obscur...

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Published inExperimental & molecular medicine Vol. 47; no. 1; p. e137
Main Authors Kim, Rae-Kwon, Suh, Yongjoon, Yoo, Ki-Chun, Cui, Yan-Hong, Kim, Hyeonmi, Kim, Min-Jung, Gyu Kim, In, Lee, Su-Jae
Format Journal Article
LanguageEnglish
Published United States Springer Nature B.V 01.01.2015
Nature Publishing Group
Subjects
Animals
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Line, Tumor
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Disease Models, Animal
Epithelial-Mesenchymal Transition - genetics
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Heterografts
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Original
Phenotype
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins p21(ras)
ras Proteins - genetics
ras Proteins - metabolism
Transcriptional Activation
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Summary:Basal-type breast cancers are among the most aggressive and deadly breast cancer subtypes, displaying a high metastatic ability associated with mesenchymal features. However, the molecular mechanisms underlying the maintenance of mesenchymal phenotypes of basal-type breast cancer cells remain obscure. Here, we report that KRAS is a critical regulator for the maintenance of mesenchymal features in basal-type breast cancer cells. KRAS is preferentially activated in basal-type breast cancer cells as compared with luminal type. By loss and gain of KRAS, we found that KRAS is necessary and sufficient for the maintenance of mesenchymal phenotypes and metastatic ability through SLUG expression. Taken together, this study demonstrates that KRAS is a critical regulator for the metastatic behavior associated with mesenchymal features of breast cancer cells, implicating a novel therapeutic target for basal-type breast cancer.
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These authors contributed equally to this work.
ISSN:2092-6413
1226-3613
2092-6413
DOI:10.1038/emm.2014.99