Distinct regulatory effect of the p34SEI-1 oncoprotein on cancer metastasis in HER2/neu-positive and -negative cells.
The p34(SEI-1) oncoprotein is involved in a transcriptional regulation, cell cycle regulation, apoptosis, development and many other important cellular functions. Our present study suggests that p34(SEI-1) can promote metastasis by enhancing migration and invasion of cancer cells. Consistently, p34(SEI-1) expression was found to be increased as the tumor invasiveness progressed in human breast tissues. p34(SEI-1) may promote cancer metastasis by activating the PI3K/AKT signaling pathway. In this process, p34(SEI-1) activates two different serine/threonine kinases, AKT or ILK, depending on the expression status of HER2/neu oncogene. In HER2/neu suppressed cancer cells, p34(SEI-1) promoted metastasis mainly by activating AKT via phosphorylation of the 473 serine residue. In HER2/neu expressing cancer cells, p34(SEI-1) overexpression downregulates HER2/neu expression, leading to the activation of another crucial serine/threonine kinase ILK due to phosphorylation of the 178 threonine residue instead of AKT. These results suggest that p34(SEI-1) affects cancer metastasis by regulating two different signaling pathways depending on the HER2/neu expression level, in which AKT and ILK modulation can be stimulated by p34(SEI-1) overexpression.
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Samil
S
Jung
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Jiyeon
J
Ohk
Department of Pathology, College of Medicine, Soonchunhyang University, Chonan 330-090, Republic of Korea.
Dongjun
D
Jeong
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Chengping
C
Li
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Soonduck
S
Lee
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Jingjing
J
Duan
Department of Pathology, College of Medicine, Soonchunhyang University, Chonan 330-090, Republic of Korea.
Changjin
C
Kim
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Jong-Seok
JS
Lim
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Young
Y
Yang
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Keun-Il
KI
Kim
Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Myeong-Sok
MS
Lee
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000099200:Scaffold Protein ILK
D009687:Nuclear Proteins; D015513:Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; D000099200:Scaffold Protein ILK; C402464:SERTAD1 protein, human