title: 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.
authors.affiliation: Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of General Surgery, Boji-Affiliated Hospital (Zengcheng People's Hospital), Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jinke
authors.initials: J
authors.lastname: Yao
authors.affiliation: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Nie
authors.affiliation: Department of Medcine, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Medcine, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang, China.
authors.forename: Pinjia
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang, China.
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Shi
authors.affiliation: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, Joint Laboratory of Laser Oncology with Cancer Center of Sun Yat-sen University, College of Biophotonics, South China Normal University, Guangzhou, China.
authors.forename: Zhengzhi
authors.initials: Z
authors.lastname: Zou
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D000072278:Forkhead Box Protein M1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D015533:Transcriptional Activation
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins
keywords: FOXM1; HSPA5; colorectal cancer; invasion; migration