Monocarboxylate transporter 4 promotes the migration of non­cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis.

The tumor microenvironment (TME) and Warburg effect are critical for the regulation of tumor metastasis. The monocarboxylate transporter (MCT) family members, particularly MCT4, which is encoded by the solute carrier family 16 member 3 gene, play an important role in the regulation of the TME and mediation of the Warburg effect by transporting lactate out of cancer cells. Migration and invasion are two key features of metastasis. Few studies have investigated the mechanism by which MCT4 promotes cell migration, and the suggested mechanisms by which MCT4 promotes migration vary in different tumor cell models. The purpose of the present study was to use non-cancerous cells as a research model to investigate the specific mechanism underlying the promotion of migration by MCT4. In a previous study, murine L929 cells overexpressing human MCT4 (MCT4-L929 cells) were generated and MCT4 was demonstrated to promote the migration and invasion of these non-cancerous cells. In the present study, MCT4-L929 cells and control-L929 cells were used to investigate the potential pathways and mechanisms through which MCT4 promotes cell migration. RNA sequencing analysis revealed 872 differentially expressed genes, comprising 337 and 535 upregulated and downregulated genes, respectively, in the MCT4-L929 cells. Reverse transcription-quantitative analysis and western blotting revealed that MCT4 overexpression increased the transcription and protein levels of insulin-like growth factor 1 (IGF1). In a wound healing assay, the migration of exogenous mouse IGF1-treated control-L929 cells was similar to that of MCT4-L929 cells. Additionally, the inhibition of IGF1 receptor (IGF1R) or serum/glucocorticoid regulated kinase 1 (SGK1), a downstream protein in the IGF1 and phosphoinositide 3-kinase PI3K regulatory subunit 3 (PIK3R3) pathways, in MCT4-L929 cells mitigated the cell migration-promoting effect of MCT4. These novel findings suggest that MCT4 may promote the migration of L929 fibroblast cells via activation of the IGF1/IGF1R/PIK3R3/SGK1 axis.

Overexpression of monocarboxylate transporter 4 promotes the migration and invasion of non-carcinogenic L929 fibroblast cells.

Metastasis is a primary contributor to the low survival rates of patients with cancer. Enhanced migration and invasion are two key features of the metastatic transformation of cancer cells. Furthermore, despite the fact that overexpression of the monocarboxylate transporter (MCT)1 and 4 proteins has been found to promote the migration or invasion of cancer cells, previous findings have not been conclusive and have even been contradictory. The majority of these previous studies have relied on the silencing or inhibition of MCT1/4 expression or function in highly metastatic cell lines. Silencing can be transient or incomplete, and inhibition can result in off-target effects. Employing a different approach, the present study stably transfected human MCT1 and MCT4 into the non-carcinogenic murine NCTC clone 929 (L929) cell line, which had undetectable endogenous MCT1 and MCT4 expression. It was observed that overexpression of MCT4, and not MCT1, promoted the migration and invasion of L929 cells. It was also found that overexpression of an inactive form of the MCT4 transporter with a single amino acid mutation failed to promote either migration or invasion, which suggested that MCT4 activity is required. Since an epidermal growth factor receptor (EGFR) inhibitor could reverse the effect of MCT4-overexpression, it was concluded that MCT4-overexpression exert its functions through modulating the EGF/EGFR pathway.

Chiral carbonaceous nanotubes containing twisted carbonaceous nanoribbons, prepared by the carbonization of chiral organic self-assemblies.

Single-handed helical silica nanotubes containing chiral organic self-assemblies were prepared by using a supramolecular templating approach. After carbonization and the removal of the silica, single-handed helical carbonaceous nanotubes that contained twisted carbonaceous nanoribbons were obtained. It is believed that the nanotubes formed as a result of the adsorption of low-molecular-weight gelators. The twisted nanoribbons were formed because of the carbonization of the organic self-assemblies. The samples were characterized by using field-emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Raman spectroscopy, and circular dichroism. For the samples carbonized at 900 °C for 3.0 h, a partially graphitized structure was identified. The circular dichroism (CD) spectra indicated that the twisted nanoribbons exhibited optical activity. The CD spectrum was simulated by using time-dependent density functional theory. The results suggested that the CD signals originated from the chiral stacking of aromatic rings.