Epithelial-mesenchymal transition induces endoplasmic-reticulum-stress response in human colorectal tumor cells

• Published in: PloS one 2014-01, Vol.9 (1), p.e87386-e87386
• Main Authors: Zeindl-Eberhart, Evelyn, Brandl, Lydia, Liebmann, Sibylle, Ormanns, Steffen, Scheel, Silvio K, Brabletz, Thomas, Kirchner, Thomas, Jung, Andreas
• Format: Article
• Language: English
• Subjects: Biology; Cancer; Cell adhesion & migration; Cell Line, Tumor; Chemoresistance; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Environmental conditions; Environmental stress; Epithelial-Mesenchymal Transition; Gastrointestinal diseases; Glucose; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Human behavior; Humans; Hypoxia; Kinases; Medical prognosis; Medicine; Mesenchyme; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Pathology; Protein folding; Proteins; Rodents; Sensors; Stem cells; Stress response; Stresses; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor cells; Tumorigenesis; Tumors; Unfolded Protein Response; Zinc Finger E-box-Binding Homeobox 1
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0087386

Tumor cells are stressed by unfavorable environmental conditions like hypoxia or starvation. Driven by the resulting cellular stress tumor cells undergo epithelial-mesenchymal transition. Additionally, cellular stress is accompanied by endoplasmic reticulum-stress which induces an unfolded protein response. It is unknown if epithelial-mesenchymal transition and endoplasmic reticulum-stress are occurring as independent parallel events or if an interrelationship exists between both of them. Here, we show that in colorectal cancer cells endoplasmic reticulum-stress depends on the induction of ZEB-1, which is a main factor of epithelial-mesenchymal transition. In the absence of ZEB-1 colorectal cancer cells cannot mount endoplasmic reticulum-stress as a reaction on cellular stress situations like hypoxia or starvation. Thus, our data suggest that there is a hierarchy in the development of cellular stress which starts with the presence of environmental stress that induces epithelial-mesenchymal transition which allows finally endoplasmic reticulum-stress. This finding highlights the central role of epithelial-mesenchymal transition during the process of tumorigenesis as epithelial-mesenchymal transition is also associated with chemoresistance and cancer stemness. Consequently, endoplasmic reticulum-stress might be a well suited target for chemotherapy of colorectal cancers.