In BMC Cancer this week, researchers at the University of Manitoba report on the effect of transglutaminase 2 phosphorylation on NF-kappaB, Akt, and PTEN expression. TG2 and its phosphorylation have been found to be upregulated in many cancer cell types, the team says. For this study, the researchers used embryonic fibroblasts from TG2-null mice to determine the effects of the phosphorylation on NF-kappaB, Akt, and PTEN, and found that the activation of protein kinase A in native TG2 overexpressing fibroblasts from the TG2-null mice resulted in an increased activation of NF-kappaB and Akt phosphorylation, compared to empty vector transfected control cells, and a downregulation of PTEN. "These effects were not observed in MEFtg2-/- cells overexpressing m[utant]-TG2," the team writes. "Furthermore, Akt activation correlated with the simultaneous activation of NF-kappaB and a decrease in PTEN suggesting that the facilitatory effect of TG2 on Akt activation occurs in a PTEN-dependent manner." This suggests that blocking TG2 phosphorylation may cause an attenuation of NF-kappaB activation and PTEN downregulation in TG2 overexpressing cancers, they add.
Researchers in Spain compare the anti-cancer effects of fatty-acid synthase inhibitors C75 and (-)-epigallocatechin-3-gallate in a model of lung cancer in BMC Cancer this week. The team evaluated the action of C75 and EGCG on FASN, cellular proliferation, apoptosis, and cell signaling in vitro as well as their anti-tumor effects in a mouse model, and found that both inhibitors have comparable effects in blocking FASN activity. However, they also found that EGCG had no significant effect on the activity of CPT enzymes, the rate-limiting enzyme of fatty acid beta-oxidation, while C75 stimulated CPT up to 130 percent. "Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling," the authors write. "While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss." This suggests that EGCG may be a candidate for pre-clinical development, they add.
Finally in BMC Cancer this week, researchers in Sweden report on their validation of podocalyxin-like protein as a biomarker of poor prognosis in patients with colorectal cancer. Using tissue microarrays with tumor samples from a retrospective cohort of 270 colorectal cancer patients and a prospective cohort of 337 colorectal cancer patients, the team found that high PODXL expression was significantly associated with unfavorable clinicopathological characteristics. In the retrospective cohort, high expression was associated with a significantly shorter five-year overall survival, and in the in the prospective cohort, it was associated with shorter time to recurrence and shorter disease-free survival. "The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients," the authors write.