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The Role for GALNT14 in the lung metastasis of breast cancer
Mi-Young Kim1,2,*
1Department of Biological Sciences and 2KAIST Institute for the BioCentury, Cancer Metastasis Control Center Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea
Aberrant expression of polypeptide N-acetyl-galactosaminyltransferases (GALNTs) has been associated with cancer, but their function(s) in metastasis remains elusive. Recently, we have identified GALNT14, one of the O-GalNAc glycosylation-initiating enzymes, as a prognostic marker for pulmonary relapses in breast cancer patients. Furthermore, we showed that GALNT14 promotes lung metastasis by novel mechanisms: 1) enhancing metastasis initiation by inhibiting anti-metastatic effect of BMPs produced from lung stroma, 2) exploiting growth signals (e.g., FGFs) supplied by macrophages for their growth into macrometastases in the lung environment. These multi-faceted roles of GALNT14 in lung metastasis are achieved by GALNT14-mediated inhibition and activation of BMP and FGF signaling pathways, respectively. The link among GALNT14, its downstream pathways and lung metastasis provides us with an opportunity to develop effective therapeutic intervention for breast cancer.
Abstract, Accepted Manuscript(in press) [Submitted on March 28, 2017, Accepted on March 28, 2017]
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