Astrocyte elevated gene‐1 interacts with β‐catenin and increases migration and invasion of colorectal carcinoma

Abstract

To investigate the astrocyte elevated gene-1 (AEG-1) expression and its relationship with the clinicopathological features of colorectal carcinoma (CRC) and β-catenin signaling pathway. Real-time PCR, Western blot, immunohistochemistry, and immunofluorescence staining were performed to detect AEG-1 expression in CRC cell lines, 8 pairs of fresh CRC and adjacent nontumor tissues (ANT), 120 pairs of paraffin-embedded CRC specimens and ANT tissues, and 60 samples of lymph node metastatic CRC tissues. Scratch wound assay and transwell matrix penetration assay were performed to determine migration and invasion of SW480 cell lines with stable AEG-1 overexpression or SW620 cell lines with AEG-1 knockdown. AEG-1 expression was upregulated in CRC cell lines and tissues compared with ANT. Furthermore, AEG-1 expression level significantly correlated with UICC stage, and the N classification. AEG-1 overexpression significantly enhanced migration and invasion of SW480 cell lines. However, AEG-1 knockdown suppressed migration and invasion of SW620 cell lines. Meanwhile, there was a positive correlation between AEG-1 high expression and β-catenin nuclear expression in CRC. AEG-1 overexpression increased nuclear β-catenin accumulation in CRC cell lines. AEG-1 knockdown decreased nuclear β-catenin accumulation in CRC cell lines. Moreover, we firstly found that AEG-1 interacted with β-catenin in SW480 cell lines. Our results for the first time showed that AEG-1 interacted with β-catenin in CRC cells and AEG-1 expression was closely associated with progression of CRC. AEG-1 might be a potential therapeutic target in CRC.

Astrocyte elevated gene-1 in relation to colorectal cancer development and radiotherapy response

“…The impact of AEG-1 on invasion, migration, and metastasis has been shown in several studies for different kinds of cancers, and we found in paper I that the expression of AEG-1 was increased in liver metastases compared with the primary CRC tumours (109,204,224,247).…”

“…However, other studies analysing the AEG-1 expression in CRC showed no or only slight nuclear expression (214,247,310,311). The differences in AEG-1 localisation between our study and the other studies performed in CRC, might be due to different antibodies and staining The AEG-1 expression did not differ between the distant normal mucosa and the adjacent mucosa, neither in the cytoplasm nor in the nucleus, and was therefore considered as one group for further analyses to increase the sample size.…”

“…The determination of these elements and the impact of mutations is very challenging. We also analysed the corresponding normal mucosa, whenever available, to be able to identify (214,247,310,311).…”

Astrocyte elevated gene-1 (AEG-1) and the A(E)Ging HIV/AIDS-HAND

“…Besides NF-κB, AEG-1 also physically interacts with a number of transcription factors and to regulate downstream pathways (Table 1). AEG-1 interacts with β-catenin to influence Wnt/β-catenin signaling in colorectal carcinoma (Zhang et al , 2013), which is critical for cytoskeletal changes that recruit astrocytes to the injury site (Yang et al , 2012). Consequent to injury/neuroinflammation, reactive astrocytes can induce rapid activation of microglial cells and release of inflammatory mediators like IL-1β and TNF-α, triggering a cascade of autocrine signaling events to amplify the neuroinflammatory barrage (Ransohoff and Tani, 1998; Tichauer et al , 2007).…”

“…Nrf-2, thus stabilized, translocates to the nucleus and regulates ARE promoter activity. AEG-1 interacts with various other proteins, including NF-κB p65 subunit, CBP, Rrs1, β-catenin and ubinuclein-1, to elicit diverse functions (Table 1) (Carnemolla et al , 2009; Lupo et al , 2012; Sarkar et al , 2008; Zhang et al , 2013). Numerous in vitro studies in cancer cell lines have demonstrated AEG-1 induction in response to oxidative stress, hypoxia and glucose deprivation, and have identified important roles in modulating survival pathways (Baumann and Dorsey, 2011; Bhutia et al , 2010; Noch et al , 2011).…”