We previously reported that integrin alpha 7 (ITGA7) was downregulated in colorectal cancer (CRC) tissues and CRC cell lines and that the lower expression of ITGA7 in CRC tissues was correlated with distant metastasis, suggesting that ITGA7 may function as a suppressor in CRC. The present research was conducted to further investigate the role and mechanisms of ITGA7 in CRC progression. First, bisulfite modification and genomic sequencing (BSP) results showed that the methylation rate of ITGA7 promoter was higher in 10 CRC tissues than in the matched normal tissues. Additionally, 5-Aza-CdR treatment increased ITGA7 expression in CRC cells. Gain-of-function assays revealed the inhibitory role of ITGA7 in CRC cell proliferation and migration. Mechanistically, RNA sequencing, RT-qPCR, and cytoplasm and nuclear separation and rescue assays indicated that knockdown of ITGA7 activated the transcription of MMP9, SETD7, and ADAM15 by enhancing the nuclear translocation of NF-κB. Moreover, CoIP and Western blot suggested a mechanistic model in which ITGA7 binds to CKAP4 to block the interaction of CKAP4 and PI3K p85α and thereby suppress the PI3K/AKT/NF-κB pathway. Accordingly, the current study suggests that ITGA7 functions as a suppressor in CRC progression and that its expression is controlled by promoter methylation.
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http://dx.doi.org/10.1016/j.bbamcr.2024.119785 | DOI Listing |
Gut Microbes
December 2025
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
The intracellular bacterium (Fn) mediates tumorigenesis and progression in colorectal cancer (CRC). However, the origin of intratumoral Fn and the role of Fn-infected immunocytes in the tumor microenvironment remain unclear. Here, we observed that Fn-infected neutrophils/macrophages (PMNs/MΦs), especially PMNs, accumulate in tumor tissues and fecal Fn abundance correlates positively with an abundance of blood PD-L1 PMNs in CRC patients.
View Article and Find Full Text PDFPharmacol Res
December 2024
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 350401, Taiwan. Electronic address:
The large and rapid increase in the incidence and mortality of colorectal cancer (CRC) demonstrates the urgent need for new drugs with higher efficacy to treat CRC. However, the lack of applicable and reliable preclinical models significantly hinders the progress of drug development. Patient-derived xenograft (PDX) models are currently considered reliable in vivo preclinical models for predicting drug efficacy in cancer patients.
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
November 2024
División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México.
Connective tissue growth factor (CTGF) and Caspase 8 (CASP8) have been implicated in cancer development and progression. Variants such as CASP8 rs3834129 (-652 6N I/D) and CTGF rs6918698 (-945 C>G) have been associated with several cancers, although their association is still debated between populations. This study investigates the possible association between the CASP8 rs3834129 and CTGF rs6918698 variants with colorectal cancer (CRC) in Mexican patients.
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
November 2024
College of Medicine, University of Duhok, Duhok, Iraq.
Colorectal cancer (CRC) is the third most frequent type of cancer and the second leading cause of cancer-related deaths globally. Despite a thorough understanding of its biology, etiology, and epidemiology, an estimated 1.8 million new cases are diagnosed each year, and 900000 people die as a result of malignancy.
View Article and Find Full Text PDFInt J Mol Med
February 2025
Department of Laboratory Medicine, Suzhou Wuzhong People's Hospital, Suzhou, Jiangsu 215128, P.R. China.
Inflammatory bowel diseases (IBDs), which encompasses Crohn's disease and ulcerative colitis, is a chronic inflammatory condition associated with an increased risk of colorectal cancer (CRC). Small RNAs have been linked to various illnesses, including IBD and CRC. These small RNAs also serve as potential biomarkers for these diseases, offering a cutting‑edge approach to investigating possible treatments.
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