HLTF suppresses the migration and invasion of colorectal cancer cells via TGF‑β/SMAD signaling in vitro

Abstract

Helicase-like transcription factor (HLTF) has been identified as a tumor suppressor gene. The hypermethylation of HTLF is frequently observed in various types of cancer, including colorectal cancer (CRC). However, the mechanisms through which HLTF suppresses CRC progression remain unclear. Thus, the aim of the present study was to explore the biological function of HLTF in CRC cells and the underlying mechanisms. CRC tissues and cells were used to detect the expression of HLTF. Wound-healing and Transwell assays were performed to assess the motility of CRC cells. The results revealed that HLTF expression was significantly associated with the differentiation status, invasion depth, lymph node metastasis and distant metastasis. A low HLTF expression was significantly associated with a poor survival. Furthermore, HTLF knockdown or ectopic overexpression significantly promoted or suppressed the motility of CRC cells, respectively. With regard to the underlying molecular mechanisms, the protein expression of HTLF was upregulated when the CRC cells were stimulated with transforming growth factor (TGF)-β, and HLTF upregulation induced an increase in SMAD4 and p-SMAD2/3 expression and a decrease in levels of the TGF-β/SMAD pathway downstream genes, Vimentin and zinc finger e-box binding homeobox 1 (ZEB1). On the whole, the findings of this study suggest that HLTF is negatively associated with the progression of CRC, and its overexpression suppresses the migration and invasion of CRC cells by targeting the TGF-β/SMAD pathway.

Helicase-like transcription factor-deletion from the tumor microenvironment in a cell line-derived xenograft model of colorectal cancer reprogrammed the human transcriptome-S-nitroso-proteome to promote inflammation and redirect metastasis

“…There is a negative correlation between HLTF expression and the progression of CRC in humans [ 11 – 16 ]. Previous studies have shown the progressive loss of HLTF from tumor cells correlates with negligible HLTF expression in the TME [ 19 , 20 ]. The CDX model is predicated on the paucity of HLTF expression in the fibroblasts of the TME as shown in a well-differentiated adenocarcinoma ( Fig 2 ) from a male patient that resulted in hemicolectomy.…”

“…Methylated HLTF DNA in serum is significantly correlated with tumor size, more aggressive tumors, advanced stage (III or IV) metastatic disease, including micro-metastasis, and shorter survival [15][16][17][18]. Progressive loss of HLTF expression from tumor cells correlates with tumor staging [19]. There are higher levels of HLTF protein in tumors from patients with early-stage 1 CRC compared to patients with late-stage IV disease.…”

Integrative modeling of multi-omics data for predicting tumor mutation burden in lung cancer patients

“…Meanwhile, it was found that LINC00958 promoted cell proliferation and migration in oral squamous cell carcinoma through miR-627-5p/YBX2 axis [58]. Helicase-like transcription factor (HLTF) was a tumor suppressor, the expression of HLTF was negatively correlated with colorectal cancer and its overexpression regulated the TGF-β/SMAD pathway to suppress the migration and invasion of CRC [59]. It was reported that the wild type alleles of kinesin light chain 3 (KLC3) Lys751Gln was signi cantly correlated with greater smoking intensity, and genetic variations may in uence the progression of lung cancer [60].…”

Effects of cisatracurium on epithelial‑to‑mesenchymal transition in esophageal squamous cell carcinoma

“…Mounting evidence has demonstrated that the TGF-β/Smad pathway is implicated in the progression of cancer through regulation of the expression of related genes (37–39). TGF-β has the ability to induce invasion, migration and EMT in a number of cancer cell types, including glioblastoma and breast cancer (40,41).…”