MTHFD1L, A Folate Cycle Enzyme, Is Involved in Progression of Colorectal Cancer

Abstract

Identification of new molecular targets is needed for the treatment of colorectal cancer (CRC). Methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L), an enzyme in the folate cycle, is involved in formate generation and therefore in one-carbon metabolism. Here, we examined the expression and the role of MTHFD1L in CRC progression. Bioinformatics analysis of several public databases showed overexpression of MTHFD1L in CRC tissues as compared to normal tissues. Quantitative real-time PCR and Western blotting revealed that expressions of MTHFD1L RNA and protein were higher in CRC tissues compared to their corresponding normal tissues of CRC patients. Immunohistochemical staining demonstrated higher cytoplasmic MTHFD1L reactivity in tumor tissues compared to paired normal tissues. Further, to determine the functional relevance of MTHFD1L, it was knocked down by an siRNA in CRC cells. Silencing of MTHFD1L inhibited CRC cell proliferation, colony formation, invasion, and migration. Thus, to our knowledge for the first time in the literature, we show that MTHFD1L is involved in CRC progression and that blocking of MTHFD1L decreases the growth of colon cancer cells, thus providing an avenue to target this enzyme with small molecule inhibitors.

Genetic Variants of HOTAIR Associated With Colorectal Cancer Susceptibility and Mortality

“…CRC is associated with a variety of factors. Representative factors include hypertension (42,43), folate (44,45), homocysteine (46), and diabetes milieus (47). Thus, treatment strategies and prognostic management methods change.…”

PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer

“…NuPAGE™ 4-12% Bis-Tris Midi Protein Gels, 20-well (Invitrogen, ThermoFisher Scientific, Carlsbad, CA, USA) were used to separate proteins, which were transferred onto Immobilon-P PVDF membranes (EMD Millipore, Billerica, MA, USA), followed by incubation for 1 hour in blocking buffer (Tris-buffered saline, 0.1% Tween [TBS-T], 5% nonfat dry milk) as described previously [58]. The membranes were incubated overnight at 4 • C with a primary antibody.…”

TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status

“…Samples of this cohort were previously evaluated for MS and p53 mutational status [26,27]. Cohort 2: Frozen specimens with corresponding normal tissues (n = 95) for quantitative PCR (qPCR) and immunoblot analysis as described previously [28]. Cohort 3: Frozen liver metastases of CRCs and matched normal liver specimens (n = 9) were used to investigate the expression of TRIP13.…”

“…As described earlier [28,29], immunoblot analyses were accomplished to evaluate TRIP13 protein expression in CRC cells. SDS/PAGE involved use of NuPAGE TM 4-12% Bis-Tris Midi Protein Gels, 20-well (Invitrogen, ThermoFisher Scientific).…”