thapsigargin and Colorectal-Neoplasms

Colorectal cancer (CRC) is the third most common tumor in the world; however, the role and mechanism of endoplasmic reticulum (ER) stress in CRC metastasis remains largely unclear. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) is a long non‑coding RNA (lncRNA), which has previously been associated with CRC metastasis. It has been suggested that ER stress pathways regulate lncRNA expression; however, the effect of ER stress on MALAT1 expression in cancer is unknown. The present study aimed to investigate the relationship between ER stress pathways, MALAT1 expression and cell migration in CRC cells. ER stress was induced by thapsigargin (TG); low dose TG induced the migration of HT29 and HCT116 cells, but not SW1116 and SW620 cells. This effect was associated with increased expression levels of MALAT1, as the knockdown of MALAT1 prevented TG‑induced cell migration. TG‑induced MALAT1 expression was associated with inositol‑requiring enzyme 1 (IRE1) expression and activation of the protein kinase R (PKR)‑like ER kinase (PERK) signaling pathway. X‑box‑binding protein 1 (XBP1) and activating transcription factor 4 (ATF4) binding sites were predicted to be located in the MALAT1 gene promoter regions and the expression of MALAT1 was positively associated with XBP1 and ATF4 expression levels in CRC tissue samples. Thus, these findings indicated that ER stress may promote the migration of CRC cells and contribute to the progression of CRC through the activation of the IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways. In conclusion, to the best of our knowledge, this study is the first report that lncRNA MALAT1 expression is regulated by the IRE1/XBP1 pathway in CRC.

Topics: Activating Transcription Factor 4; Cell Line, Tumor; Cell Movement; Colorectal Neoplasms; Endoplasmic Reticulum Stress; Enzyme Inhibitors; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; RNA, Long Noncoding; Thapsigargin; Transcriptional Activation; X-Box Binding Protein 1

Menin is a nuclear epigenetic regulator that can both promote and suppress tumor growth in a highly tissue-specific manner. The role of menin in colorectal cancer, however, remains unclear. Here, we demonstrate that menin was overexpressed in colorectal cancer and that inhibition of menin synergized with small-molecule inhibitors of EGFR (iEGFR) to suppress colorectal cancer cells and tumor xenografts

Topics: Animals; Apoptosis; Biomarkers, Tumor; Calcium; Cell Proliferation; Colorectal Neoplasms; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; ErbB Receptors; Female; Gefitinib; Gene Expression Regulation, Neoplastic; Humans; Inositol 1,4,5-Trisphosphate Receptors; Mice; Mice, Nude; Protein Kinase Inhibitors; Proto-Oncogene Proteins; S-Phase Kinase-Associated Proteins; Thapsigargin; Tumor Cells, Cultured; Xenograft Model Antitumor Assays