Pathways of proliferation and antiapoptosis driven in breast cancer stem cells by stem cell protein piwil2.
Cancer stem cell studies may improve understanding of tumor pathophysiology and identify more effective strategies for cancer treatment. In a variety of organisms, Piwil2 has been implicated in multiple roles including stem cell self-renewal, RNA silencing, and translational control. In this study, we documented specific expression of the stem cell protein Piwil2 in breast cancer with predominant expression in breast cancer stem cells. In patients who were evaluated, we determined that 90% of invasive carcinomas and 81% of carcinomas in situ exhibited highest expression of Piwil2. In breast cancer cells, Piwil2 silencing suppressed the expression of signal transducer and activator of transcription 3, a pivotal regulator of Bcl-X(L) and cyclin D1, whose downregulation paralleled a reduction in cell proliferation and survival. Our findings define Piwil2 and its effector signaling pathways as key factors in the proliferation and survival of breast cancer stem cells.
Lee
Jae Ho
JH
North East England Stem Cell Institute, Institute of Human Genetics, and Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
Jung
Cornelia
C
Javadian-Elyaderani
Parisa
P
Schweyer
Stefan
S
Schütte
Dorothea
D
Shoukier
Moneef
M
Karimi-Busheri
Feridoun
F
Weinfeld
Michael
M
Rasouli-Nia
Aghdass
A
Hengstler
Jan G
JG
Mantilla
Alejandra
A
Soleimanpour-Lichaei
Hamid Reza
HR
Engel
Wolfgang
W
Robson
Craig N
CN
Nayernia
Karim
K
D017209:Apoptosis / Q000502:physiology; D060565:Argonaute Proteins; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D051020:bcl-X Protein / Q000378:metabolism
D060565:Argonaute Proteins; C494811:BCL2L1 protein, human; C486868:PIWIL2 protein, human; D011506:Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051020:bcl-X Protein