title: Persistent activation of STAT3 by PIM2-driven positive feedback loop for epithelial-mesenchymal transition in breast cancer.
abstract: Metastasis of breast cancer is promoted by epithelial-mesenchymal transition (EMT). Emerging evidence suggests that STAT3 is a critical signaling node in EMT and is constitutively activated in many carcinomas, including breast cancer. However, its signaling mechanisms underlying persistent activation of STAT3 associated with EMT remain obscure. Here, we report that PIM2 promotes activation of STAT3 through induction of cytokines. Activation of STAT3 caused an increase in PIM2 expression, implicating a positive feedback loop between PIM2 and STAT3. In agreement, targeting of either PIM2, STAT3 or PIM2-dependent cytokines suppressed EMT-associated migratory and invasive properties through inhibition of ZEB1. Taken together, our findings identify the signaling mechanisms underlying the persistent activation of STAT3 and the oncogenic role of PIM2 in EMT in breast cancer.
authors: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors: Nizam
authors: N
authors: Uddin
authors: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors: Rae-Kwon
authors: RK
authors: Kim
authors: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors: Ki-Chun
authors: KC
authors: Yoo
authors: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors: Young-Heon
authors: YH
authors: Kim
authors: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors: Yan-Hong
authors: YH
authors: Cui
authors: Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon, Korea.
authors: In-Gyu
authors: IG
authors: Kim
authors: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors: Yongjoon
authors: Y
authors: Suh
authors: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors: Su-Jae
authors: SJ
authors: Lee
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: C508606:CXCL8 protein, human; D018398:Homeodomain Proteins; D053582:Interleukin-1alpha; D016209:Interleukin-8; C490587:PIM2 protein, human; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D017346:Protein Serine-Threonine Kinases
keywords: Cytokines; PIM2; STAT3; epithelial-mesenchymal transition; positive feedback loop