FOXM1 promotes invasion and migration of colorectal cancer cells partially dependent on HSPA5 transactivation

Abstract

In this study, to investigate whether endoplastic reticulum (ER) stress correlated with FOXM1 in colorectal cancer, we analysed the mRNA levels of FOXM1 and ER stress markers HSPA5 and spliced XBP1 by qRT-PCR. FOXM1 mRNA levels were found to positively correlate with HSPA5 in colorectal cancer. However, no significant correlation between FOXM1 and spliced XBP1 mRNA levels was found. Theses results suggested the positive correlation between FOXM1 and HSPA5 in colorectal cancer was not associated with ER stress. Next, we provided evidences that FOXM1 promoted HSPA5 transcription by directly binding to and stimulating HSPA5 promoter. Moreover, a FOXM1-binding site mapped between -1019 and -1012 bp of the proximal HSPA5 promoter was identified. In addition, we found that enhancement of cell migration and invasion by FOXM1 was significantly attenuated by depletion of HSPA5 in colorectal cancer cell. Furthermore, FOXM1 triggered colorectal cancer cell migration and invasion was involved in activities of cell-surface HSPA5. Lastly, our results suggested FOXM1 facilitated the activities and expressions of MMP2 and 9 associated with cell-surface HSPA5 in colorectal cancer cells. Moreover, statistically significant positive correlations between FOXM1 and MMP2 mRNA expression, between HSPA5 and MMP2 were found in colorectal cancer tissue specimens. Together, our results suggested that FOXM1-HSPA5 signaling might be considered as a novel molecular target for designing novel therapeutic regimen to control colorectal cancer metastasis and progression.

A novel integrative risk index of papillary thyroid cancer progression combining genomic alterations and clinical factors

“…In particular, we found PTC progression was significantly associated with up-regulation of the FOXM1 signaling pathway. FOXM1 is a transcription factor that promotes tumorigenesis [46, 47], uncontrolled cell growth, and epithelial-mesenchymal transition [48, 49]; it has been linked to the progression of ovarian cancer [50], colorectal cancer [51], triple negative breast cancer [52], non-small cell lung cancer [53], and stomach cancer [54]. Consistent with previous reports [14, 15], our findings suggest that the FOXM1 pathway also may provide therapeutic targets to prevent PTC progression.…”

Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression

“…All of the samples were retrieved within 15 min after the surgery and immediately frozen at −80 °C until used for gene expression analysis as previously described. 41 This study was approved by the Clinical Ethics Review Board at The First Affiliated Hospital of Xi'an Jiaotong University and written informed consents were from all patients at their recruitment time.…”

Overriding Elements in Colon Cancer Progression: Some Less Known Facts

“…Additionally, Forkhead Box M1 (FOXM1) also advances EMT as FOXM1 promotes urokinase-type plasminogen activator receptor (uPAR) and matrix metalloproteinase 2 & 9. 8 In the condition of CRC, endoplasmic reticulum (ER) stress is down-regulated by hypoxic condition thereby increasing the aggression of metastasis. It was clearly observed in several solid tumors that FOXM1 transcrip-tion factor was over expressed and ER stress was far reduced.…”

“…It was clearly observed in several solid tumors that FOXM1 transcrip-tion factor was over expressed and ER stress was far reduced. 8 The condition of hypoxia can be attenuated either by sensitizing the cancerous cells to ER stress or blocking uPAR pathway. Figure 1 depicts the role of hypoxia in regulating mammalian target of rapamycin (mTOR) in articulating vascular proliferation.…”