title: Elevated TGF-β1 and -β2 expression accelerates the epithelial to mesenchymal transition in triple-negative breast cancer cells.
abstract: The epithelial-mesenchymal transition (EMT) is a key process in tumor invasion and migration. Transforming growth factor-βs (TGF-βs) are multifunctional growth factors and powerful modulators of the EMT. Here, we investigated the relationship between TGF-β expression and invasion by treated triple-negative breast cancer (TNBC) cells. Our results show that invasion capacity of TNBC cells was markedly higher than that of non-TNBC cells. In addition, EMT-related gene signatures, including vimentin (vim), fibronectin (FN), snail, and slug were highly expressed in TNBC cells. Interestingly, our results show that TGF-β1 and β2 mRNA expression levels were higher in TNBC cells than those in non-TNBC cells. Thus, we examined the effect of the TGF-β receptor I/II inhibitor LY2109761 on EMT-related gene expression and cell motility. Our data show that vim, FN, and slug mRNA expression levels dose-dependently decreased in response to LY2109761. TNBC cell motility also decreased in response to LY2109761. Finally, we investigated the effect of LY2109761 on TGF-β1 or TGF-β2-induced E-cadherin (E-cad), vim, and FN mRNA and protein expression. The reduction in E-cad and induction of vim and FN expression by TGF-β1 or TGF-β2 were completely reversed by LY2109761 treatment in HCC1806 TNBC cells. Taken together, we demonstrated that elevated TGF-β expression triggers invasion and migration by TNBCs through the EMT process. Inhibiting the TGF-β signaling pathway is considered a promising therapeutic strategy for treating TNBC.
authors.affiliation: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Electronic address: sangmin3005.kim@samsung.com.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Myeongjin
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Electronic address: paojlus@hanmail.net.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D011720:Pyrazoles / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing
chemical_list: D005353:Fibronectins; C530108:LY2109761; D011720:Pyrazoles; D011758:Pyrroles; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D014746:Vimentin
keywords: Cell invasion; Cell migration; Epithelial–mesenchymal transition; TGF-β; Triple-negative breast cancer