DCLK1 promotes epithelial‐mesenchymal transition via the PI3K/Akt/NF‐κB pathway in colorectal cancer. Issue 10 (12th January 2018)

• Record Type: Journal Article
• Authors: Liu, Weiying; Wang, Shixing; Sun, Qi; Yang, Zhen; Liu, Min; Tang, Hua
• Is Part Of: International journal of cancer. Volume 142:Issue 10(2018)
• Page Start: 2068
• Page End: 2079
• Publication Date: 2018-01-12
• Subjects: double cortin‐like kinase 1 -- colorectal cancer -- epithelial‐mesenchymal transition -- NF‐κB -- PI3K/Akt pathway; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31232
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Double cortin‐like kinase 1 (DCLK1) plays important roles during the epithelial‐mesenchymal transition (EMT) process in human colorectal cancer (CRC). However, the role of DCLK1 in regulating the EMT of CRC is still poorly understood. In this study, we report evidence that DCLK1 acts as a potent oncogene to drive its extremely malignant character of EMT in an NF‐κB‐dependent manner in CRC cells. Mechanistic investigations showed that DCLK1 induced the NF‐κBp65 subunit expression through the PI3K/Akt/Sp1 axis and activated NF‐κBp65 through the PI3K/Akt/IκBα pathway during the EMT of CRC cells. Moreover, we found that silencing the expression of DCLK1 inhibited the invasion and metastasis of CRC cells in vivo . Collectively, our findings identify DCLK1 as a pivotal regulator of an EMT axis in CRC, thus implicating DCLK1 as a potential therapeutic target for CRC metastasis. Abstract : What's new? A change in tumor cells called "epithelial‐mesenchymal transition" (EMT) helps certain types of tumors to metastasize. In this study of colorectal cancer (CRC), the authors found that an enzyme called DCLK1 acts as a potent oncogene to drive EMT, via NF‐κBp65 induction. They, then, further identified the molecular pathways involved in this event regulated through PI3K/Akt pathway. Finally, they found that silencing DCLK1 expression could inhibit metastasis of CRC cells in vivo . These results suggest that DCLK1 may offer a potential therapeutic target for metastatic CRC.