DCLK1 promotes epithelial-mesenchymal transition via the PI3K/Akt/NF-κB pathway in colorectal cancer
Authors: Hua Tang
Zhen Yang
Weiying Liu
Shixing Wang
Qi Sun
Min Liu
Journal: International Journal of Cancer (2018)
Discipline: CLINICAL MEDICINE
Keywords: NF-κB; PI3K/Akt pathway; colorectal cancer; double cortin-like kinase 1; epithelial-mesenchymal transition.
Affiliations: Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

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. 

Retracted: Yes

PubPeer comments:
 There is no mention of any negative control for either of the tests. The threshold for the ELISA test is the one indicated by the manufacturer, but actually less than 7% of the ELISA positive tests are also positive for the neutralization test (data from figure 2). The neutralization test was calibrated in another publication (reference 6 of the article), but the protocol is not described in detail in that publication (for instance, no mention of the quantity of serum used). 9 out of the 13 early samples with both tests positive are at the limit for positivity for the neutralization assay. There is no data on how many samples were tested for the neutralizing assay. If I understand correctly the sentence  all positive ELISA-S were confirmed by SN testing , all samples positive for ELISA were subsequently tested for neutralization. But on Figure 2, there are samples that are not ELISA positive, and are positive for neutralization, thus there were also samples negative for ELISA which were tested for the neutralization assay. Which proportion of samples negative for ELISA were also tested for neutralization? The absence of negative controls in this study make that there is no point of reference for the rate of false positives. , 
 Fig 1: in November they have 1% of Elisa-S positive, on Jan 06 they have 5%, followed by a 5-6% plateau up to mid-March. Fig 2: they tested all the Elisa-S positive and indeterminate with a microneutralization assay. When counting only the samples that are both Elisa and microneutralization positive we don t see any dramatic increase in prevalence. They didn t test outside of this November-March period whereas it seems they had the samples up to 2012. No negative control. The problem is that the curves don t match with the previous knowledge on the pandemic. So the data might suggest there is a problem somewhere. Did the authors run any subsequent investigations to check for consistency, maybe some unpublished negative and positive controls? Can the authors share the raw (anonymized, only the dates) results for the two assays? ,