title: GALNT14 promotes lung-specific breast cancer metastasis by modulating self-renewal and interaction with the lung microenvironment.
abstract: Some polypeptide N-acetyl-galactosaminyltransferases (GALNTs) are associated with cancer, but their function in organ-specific metastasis remains unclear. Here, we report that GALNT14 promotes breast cancer metastasis to the lung by enhancing the initiation of metastatic colonies as well as their subsequent growth into overt metastases. Our results suggest that GALNT14 augments the self-renewal properties of breast cancer cells (BCCs). Furthermore, GALNT14 overcomes the inhibitory effect of lung-derived bone morphogenetic proteins (BMPs) on self-renewal and therefore facilitates metastasis initiation within the lung microenvironment. In addition, GALNT14 supports continuous growth of BCCs in the lung by not only inducing macrophage infiltration but also exploiting macrophage-derived fibroblast growth factors (FGFs). Finally, we identify KRAS-PI3K-c-JUN signalling as an upstream pathway that accounts for the elevated expression of GALNT14 in lung-metastatic BCCs. Collectively, our findings uncover an unprecedented role for GALNT14 in the pulmonary metastasis of breast cancer and elucidate the underlying molecular mechanisms.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejon 305-701, Korea.
authors.forename: Ki-Hoon
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejon 305-701, Korea.
authors.forename: Mi So
authors.initials: MS
authors.lastname: Park
authors.affiliation: Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Tulip S
authors.initials: TS
authors.lastname: Nandu
authors.affiliation: Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Shrikanth
authors.initials: S
authors.lastname: Gadad
authors.affiliation: Department of Biomedical Informatics, Center for Genome Science, National Institute of Health, KCDC, Choongchung-Buk-do 363-951, Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejon 305-701, Korea.|KAIST Institute for the BioCentury, Cancer Metastasis Control Center, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kim
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D052004:Bone Morphogenetic Protein Receptors / Q000037:antagonists & inhibitors; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D003959:Diamines / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006031:Glycosylation; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008168:Lung / Q000473:pathology / Q000502:physiology; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051880:Receptors, Notch / Q000037:antagonists & inhibitors; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000494:pharmacology; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D001549:Benzamides; D052004:Bone Morphogenetic Protein Receptors; D003959:Diamines; D004149:Dioxoles; D020662:Guanine Nucleotide Exchange Factors; D017350:N-Acetylgalactosaminyltransferases; D011720:Pyrazoles; D011804:Quinolines; D051880:Receptors, Notch; D018125:Receptors, Transforming Growth Factor beta; D013844:Thiazoles; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000612000:24-diamino-5-phenylthiazole; C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C583032:DMH1 compound; C400705:SERGEF protein, human