A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression.
Epithelial-to-mesenchymal transition (EMT) plays an important role during normal embryogenesis, and it has been implicated in cancer invasion and metastasis. Here, we report that Ladybird homeobox 1 (LBX1), a developmentally regulated homeobox gene, directs expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor beta2 (TGFB2). In mammary epithelial cells, overexpression of LBX1 leads to morphological transformation, expression of mesenchymal markers, enhanced cell migration, increased CD44(high)/CD24(low) progenitor cell population, and tumorigenic cooperation with known oncogenes. In human breast cancer, LBX1 is up-regulated in the unfavorable estrogen receptor (ER)/progesterone (PR)/HER2 triple-negative basal-like subtype. Thus, aberrant expression of LBX1 may lead to the activation of a developmentally regulated EMT pathway in human breast cancer.
Yu
Min
M
Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Smolen
Gromoslaw A
GA
Zhang
Jianmin
J
Wittner
Ben
B
Schott
Benjamin J
BJ
Brachtel
Elena
E
Ramaswamy
Sridhar
S
Maheswaran
Shyamala
S
Haber
Daniel A
DA
D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology*; D051927:CD24 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism; D009857:Oncogenes / Q000502:physiology; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D015854:Up-Regulation; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000099254:Organic Cation Transporter 3
D051927:CD24 Antigen; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D027701:Organic Cation Transport Proteins; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053781:Transforming Growth Factor beta2; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000099254:Organic Cation Transporter 3; C542809:LBX1 protein, human; C000604407:SNAI1 protein, human; C509041:TGFB2 protein, human; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human