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Open AccessArticle

JNK Pathway Mediates Low Oxygen Level Induced Epithelial–Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer Cells

Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong, China
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Authors to whom correspondence should be addressed.
Cancers 2020, 12(1), 224; https://doi.org/10.3390/cancers12010224
Received: 23 December 2019 / Revised: 10 January 2020 / Accepted: 14 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue Microenvironment and Cancer Progression)
(1) Background: Epithelial–mesenchymal transition (EMT) and cancer cell stemness maintenance (SM) are important factors for cancer metastasis. Although hypoxia has been considered as a possible factor for EMT induction and promotion of SM, studies in this area, apart from hypoxia-inducible factor (HIF) pathways and severe hypoxia, are scant. This study aimed to evaluate the effects of different oxygen levels on EMT induction and SM and elucidate the signaling pathways involved in colorectal cancer cells. (2) Methods: Cell morphological analysis, migration assay, immunofluorescence staining of cytoskeleton and Western blotting were performed on human colorectal cancer cells HT-29, DLD-1, and SW-480 cultured at 1%, 10%, and normal (21%) O2 levels. The role played by c-Jun N-terminal kinase (JNK) was evaluated through the use of the specific JNK inhibitor SP600125. (3) Results: This study evaluated 1% and 10% O2 are possible conditions for EMT induction and SM. This study also demonstrated the partial relieve of EMT induction and SM by SP600125, showing the importance of the JNK pathway in these processes. Furthermore, this study proposed a novel pathway on the regulation of Akt by JNK-c-Jun. (4) Conclusions: This study suggests 10% O2 as another possible condition for EMT induction, and SM and JNK pathways play important roles in these processes through multiple factors. Inhibition of JNK could be explored as treatment for inhibiting metastasis in colorectal cancer cells. View Full-Text
Keywords: Akt; colorectal cancer; epithelial–mesenchymal transition; hypoxia; JNK; oxygen level; stemness maintenance Akt; colorectal cancer; epithelial–mesenchymal transition; hypoxia; JNK; oxygen level; stemness maintenance
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Tam, S.Y.; Wu, V.W.; Law, H.K. JNK Pathway Mediates Low Oxygen Level Induced Epithelial–Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer Cells. Cancers 2020, 12, 224.

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