A partial epithelial-mesenchymal transition signature for highly aggressive colorectal cancer cells that survive under nutrient restriction
Issued Date
2024-01-01
Resource Type
ISSN
00223417
eISSN
10969896
Scopus ID
2-s2.0-85182716002
Journal Title
Journal of Pathology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Pathology (2024)
Suggested Citation
Pastorino G.A., Sheraj I., Huebner K., Ferrero G., Kunze P., Hartmann A., Hampel C., Husnugil H.H., Maiuthed A., Gebhart F., Schlattmann F., Gulec Taskiran A.E., Oral G., Palmisano R., Pardini B., Naccarati A., Erlenbach-Wuensch K., Banerjee S., Schneider-Stock R. A partial epithelial-mesenchymal transition signature for highly aggressive colorectal cancer cells that survive under nutrient restriction. Journal of Pathology (2024). doi:10.1002/path.6240 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95619
Title
A partial epithelial-mesenchymal transition signature for highly aggressive colorectal cancer cells that survive under nutrient restriction
Corresponding Author(s)
Other Contributor(s)
Abstract
Partial epithelial-mesenchymal transition (p-EMT) has recently been identified as a hybrid state consisting of cells with both epithelial and mesenchymal characteristics and is associated with the migration, metastasis, and chemoresistance of cancer cells. Here, we describe the induction of p-EMT in starved colorectal cancer (CRC) cells and identify a p-EMT gene signature that can predict prognosis. Functional characterisation of starvation-induced p-EMT in HCT116, DLD1, and HT29 cells showed changes in proliferation, morphology, and drug sensitivity, supported by in vivo studies using the chorioallantoic membrane model. An EMT-specific quantitative polymerase chain reaction (qPCR) array was used to screen for deregulated genes, leading to the establishment of an in silico gene signature that was correlated with poor disease-free survival in CRC patients along with the CRC consensus molecular subtype CMS4. Among the significantly deregulated p-EMT genes, a triple-gene signature consisting of SERPINE1, SOX10, and epidermal growth factor receptor (EGFR) was identified. Starvation-induced p-EMT was characterised by increased migratory potential and chemoresistance, as well as E-cadherin processing and internalisation. Both gene signature and E-cadherin alterations could be reversed by the proteasomal inhibitor MG132. Spatially resolving EGFR expression with high-resolution immunofluorescence imaging identified a proliferation stop in starved CRC cells caused by EGFR internalisation. In conclusion, we have gained insight into a previously undiscovered EMT mechanism that may become relevant when tumour cells are under nutrient stress, as seen in early stages of metastasis. Targeting this process of tumour cell dissemination might help to prevent EMT and overcome drug resistance. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.