Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo.
BACKGROUND
The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT).


METHODS
We used xenograft models of human cancer cells in immunocompromised mice, profiling the harvested tumors separately with species-specific probes and computationally analyzing the results.


RESULTS
Here we show that human cancer cells express in vivo a precise multi-cancer invasion-associated gene expression signature that prominently includes many EMT markers, among them the transcription factor Slug, fibronectin, and α-SMA. We found that human, but not mouse, cells express the signature and Slug is the only upregulated EMT-inducing transcription factor. The signature is also present in samples from many publicly available cancer gene expression datasets, suggesting that it is produced by the cancer cells themselves in multiple cancer types, including nonepithelial cancers such as neuroblastoma. Furthermore, we found that the presence of the signature in human xenografted cells was associated with a downregulation of adipocyte markers in the mouse tissue adjacent to the invasive tumor, suggesting that the signature is triggered by contextual microenvironmental interactions when the cancer cells encounter adipocytes, as previously reported.


CONCLUSIONS
The known, precise and consistent gene composition of this cancer mesenchymal transition signature, particularly when combined with simultaneous analysis of the adjacent microenvironment, provides unique opportunities for shedding light on the underlying mechanisms of cancer invasiveness as well as identifying potential diagnostic markers and targets for metastasis-inhibiting therapeutics.
Center for Computational Biology and Bioinformatics, Columbia University, New York, NY, USA. da8@columbia.edu
Dimitris
D
Anastassiou
Viktoria
V
Rumjantseva
Weiyi
W
Cheng
Jianzhong
J
Huang
Peter D
PD
Canoll
Darrell J
DJ
Yamashiro
Jessica J
JJ
Kandel
D000818:Animals; D045744:Cell Line, Tumor; D024161:Collagen Type XI / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000071250:Snail Family Transcription Factors; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism*
D024161:Collagen Type XI; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors