Abstract
BackgroundDEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures. It plays an important role in development and progression of different types of cancer. This study aims to analyze the role of DEK in metastatic colorectal cancer.MethodsBaseline DEK expression was firstly quantified in 9 colorectal cell lines and normal mucosa by WB. SiRNA-mediated DEK inhibition was carried out for transient DEK silencing in DLD1 and SW620 to dissect its role in colorectal cancer aggressiveness. Irinotecan response assays were performed with SN38 over 24 hours and apoptosis was quantified by flow cytometry. Ex-vivo assay was carried out with 3 fresh tumour tissues taken from surgical resection and treated with SN38 for 24 hours. DEK expression was determined by immunohistochemistry in 67 formalin-fixed paraffin-embedded tumour samples from metastatic colorectal cancer patients treated with irinotecan-based therapy as first-line treatment.ResultsThe DEK oncogene is overexpressed in all colorectal cancer cell lines. Knock-down of DEK on DLD1 and SW620 cell lines decreased cell migration and increased irinotecan-induced apoptosis. In addition, low DEK expression level predicted irinotecan-based chemotherapy response in metastatic colorectal cancer patients with KRAS wild-type.ConclusionsThese data suggest DEK overexpression as a crucial event for the emergence of an aggressive phenotype in colorectal cancer and its potential role as biomarker for irinotecan response in those patients with KRAS wild-type status.
Highlights
DEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures
We propose its potential use as a marker of irinotecan-based chemotherapy response in metastatic colorectal cancer patients
DEK downregulation significantly decreased cell viability and migration DEK protein levels were analyzed in a panel of 9 humanderived Colorectal cancer (CRC) cell lines and compared with the expression in 2 non-tumor mucosa tissues
Summary
DEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures It plays an important role in development and progression of different types of cancer. DEK was identified as a fusion protein with the CAN nucleoporin due to the translocation t(6;9) in a subtype of acute myeloid leukaemia [13] It was later described as a transcription factor overexpressed in multiple neoplasms including bladder cancer [14], breast cancer [15], glioblastoma [16], hepatocellular carcinoma [17], melanoma [18], retinoblastoma [19,20], colorectal cancer [21,22] and other types of cancer, such as oral, ovarian, or uterine cervical cancer [21,23,24,25]
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