Knockdown of Beclin‐1 impairs epithelial‐mesenchymal transition of colon cancer cells

Abstract

Activation of autophagy significantly affects cancer cell behaviors, such as proliferation, differentiation, and invasiveness. Epithelial-to-mesenchymal transition (EMT) as an initial step of malignant transformation of cancer cells was linked to the activation of autophagy, but the detailed molecular mechanisms are still unknown. The present study investigates the effects of Beclin-1, a key molecule involved in activation of autophagy, on EMT of colon cancer cells. The normal colon epithelia cell line of CCD-18Co and six colon cancer cell lines with different expression levels of Beclin-1 were used in this study. The activation of autophagy and EMT markers of cancer cells were monitored by Western blotting and quantitative real-time PCR assay in the presence or absence of rapamycin (autophagy activator) and 3-MA (autophagy inhibitor). The expression of Beclin-1 in selected cell lines was modulated using small interfering RNA, and consequentially EMT markers, and cancer cell behaviors including migration and invasion, were also explored. Activation or inhibition of autophagy in colon cancer cells had positive or negative impacts on the expression of EMT markers and malignant behaviors such as cell migration and invasion. Knockdown of beclin-1 by siRNA apparently inhibited the activation of autophagy induced by rapamycin, consequentially resulted in suppression of EMT and attenuation of invasiveness of colon cancer cells. The results in this study demonstrated an association between activation of autophagy and EMT in colon cancer cells. The results showed suppression of Beclin-1 expression significantly reduced EMT and invasive behaviors in colon cancer cells.

Autophagic flux disruption contributes to Ganoderma lucidum polysaccharide-induced apoptosis in human colorectal cancer cells via MAPK/ERK activation

“…Although suggested as a tumor suppressor gene, role of Belin-1 in cancer is very complicated and controversial 64 . Recent studies reported that deletion of Beclin-1 expression by RNAi promoted apoptosis in CRC cells 65,66 . Clinical studies have reported that high expression of Beclin-1 in human advanced colorectal cancer tumors is negativity correlated with the survival rate of patients 67 .…”

The importance of epithelial-mesenchymal transition and autophagy in cancer drug resistance

“…In gastric cancer cells, autophagy inhibition promotes EMT and alters the metabolic phenotype of cells, and this is dependent on ROS-NF-κB-HIF-1α [38] . In colon cancer cells, Beclin-1 has been shown to be associated with EMT and invasive behaviours; loss of Beclin-1 was able to reverse this phenotype [41] . As described above, autophagy has a dual role: in pancreatic ductal adenocarcinoma cells, TGF-β1 induced autophagy in SMAD4-positive cells and inhibited migration by reducing nuclear translocation of SMAD family member 4 (SMAD4), whereas, in SMAD4-negative cells, migration was increased through mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) [42] .…”

Liquiritin represses proliferation , migration and invasion of colorectal cancer cells through inhibition of the miR-671/HOXB3 signaling pathway

“…3D). In addition, epithelial-mesenchymal transformation (EMT) plays an important role in the occurrence, development and metastasis of tumors [28,29]. Key transcription factors, including E-cadherin, Ncadherin and vimentin, are extensively involved in the regulation of the EMT process [30].…”