Ras activation contributes to the maintenance and expansion of Sca-1pos cells in a mouse model of breast cancer.
The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer and cause cancer metastasis and recurrence. In this study, we examined whether Ras signaling is associated with stemness of the CSCs population characterized by the stem cell antigen (Sca-1) phenotype in a 4T1 syngeneic mouse model of breast cancer. The Sca-1(pos) putative CSCs had high levels of activated Ras and phosphorylated MEK (p-MEK), compared with counterparts. The Ras farnesylation inhibitor (FTI-277) suppressed the maintenance and expansion of CSCs. Therefore, selective inhibition of Ras activation may be useful for stem-specific cancer therapy.
Kim
Ran-Ju
RJ
Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Research Institute, Gachon University of Medicine and Science, Incheon, South Korea.
Kim
Soo-Rim
SR
Roh
Kyung-Jin
KJ
Park
Sang-Bum
SB
Park
Jeong-Ran
JR
Kang
Kyung-Sun
KS
Kong
Gu
G
Tang
Binwu
B
Yang
Yu-An
YA
Kohn
Ethan A
EA
Wakefield
Lalage M
LM
Nam
Jeong-Seok
JS
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017368:Protein Prenylation; D015398:Signal Transduction; D018874:Spheroids, Cellular; D018631:ras Proteins / Q000378:metabolism*
D000950:Antigens, Ly; D004791:Enzyme Inhibitors; C096856:FTI 277; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D008715:Methionine; D000444:Aldehyde Dehydrogenase; D051231:Farnesyltranstransferase; D020930:MAP Kinase Kinase Kinases; D018631:ras Proteins