TrkC plays an essential role in breast tumor growth and metastasis

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Authors: Wook Jin ; Gyoung Mi Kim ; Min Soo Kim ; Mi Hee Lim ; Chohee Yun ; Joon Jeong ; Jeong-Seok Nam ; Seong-Jin Kim

MeSH: Animals ; Blotting, Western ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology* ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Ductal, Breast/secondary* ; Cell Adhesion ; Cell Movement ; Cell Proliferation ; Female ; Fluorescent Antibody Technique ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/secondary* ; Mice ; Mice, Inbred BALB C ; RNA, Messenger/genetics ; RNA, Small Interfering/pharmacology ; Receptor, trkC/physiology* ; Reverse Transcriptase Polymerase Chain Reaction

Keywords: breast neoplasms ; neoplasm metastasis ; neurotrophic tyrosine kinase receptor type 3 ; tumor growth

Abstract: Tropomyosin-related kinase (Trk) C, a member of the Trk family of neurotrophin receptors, has been implicated in the growth and survival of human cancer tissues. Here, we report that TrkC is frequently overexpressed in human breast cancers and plays an essential role in tumor growth and metastasis. Ectopic expression of TrkC in non-malignant mammary epithelial cells suppressed anoikis, which correlated with activation of the Ras-mitogen-activated protein kinase and phosphatidylinositol-3-OH kinase (PI3K)/Akt pathways, and reduced expression of the metastatic regulator Twist. Furthermore, suppression of TrkC expression in highly metastatic mammary carcinoma cells inhibited their growth in vitro, as well as their ability to metastasize from the mammary gland to the lung in vivo. These results have identified TrkC as a critical regulator of breast cancer cell growth and metastasis.