Heregulin-beta1 promotes metastasis of breast cancer cell line SKBR3 through upregulation of Snail and induction of epithelial-mesenchymal transition.
HRG-beta1 stimulation of breast cancer cell line SKBR3 resulted in not only increased cell migration and invasion, upregulation of some mesenchymal markers, and downregulation of epithelial marker, but also upregulation of transcription factor Snail and its nuclear translocation. Similar results were acquired for cells transfected with Snail cDNA. Furthermore, downregulation of Snail by siRNA attenuated HRG-beta1 induced EMT-like phenotype. Inhibition of Akt kinase activation by a PI3K inhibitor LY294002, or exogenous expression of a kinase-dead mutant of Akt abrogated the increase of Snail expression induced by HRG-beta1. Conversely, expression of a constitutively active Akt resulted in increase of Snail expression. These results indicated that Snail upregulation by HRG-beta1 is mediated via the PI3K/Akt signaling pathway and that Snail plays a key role in HRG-beta1 induced breast cancer cell metastasis through induction of EMT.
Cheng
Liansheng
L
School of Life Science, University of Science and Technology of China, Hefei 230027, China. charlson@ustc.edu.cn
Zha
Zhao
Z
Lang
Bo
B
Liu
Jing
J
Yao
Xuebiao
X
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002633:Chemotaxis; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D009025:Morpholines / Q000494:pharmacology; D009362:Neoplasm Metastasis; D020890:Neuregulin-1 / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis*
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D020890:Neuregulin-1; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C087230:heregulin beta1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt