Background: Metabolic reprogramming and epithelial-mesenchymal transformation (EMT) play an important role in lung cancer. In recent studies, metabolic enzymes such as Fructose-1,6-bisphosphatase 1 (FBP1) have shown potential functions beyond regulating metabolism.Methods: Western blot assay was performed to detect glycolysis-related and EMT-related protein expression levels. The glucose uptake kit and adenosine triphosphate (ATP) detection kit were used to detect glucose uptake rate and ATP content. Transwell assay was used to determine the invasiveness of lung adenocarcinoma cells. Wound healing assay was used to determine the metastatic ability of lung adenocarcinoma cells. Methyl thiazolyl tetrazolium (MTT) assay and EdU staining were performed to investigate the effect of FBP1 overexpression on lung adenocarcinoma proliferation.Results: Overexpression of FBP1 down-regulated glycolysis-related protein levels and inhibited glucose uptake and ATP production, while knockdown of FBP1 had the opposite effect. Overexpression of FBP1 reversed EMT and inhibited Slug expression. Meanwhile, overexpression of FBP1 impaired the invasion, metastasis and proliferation ability of lung adenocarcinoma cells. In contrast, FBP1 knockdown promoted the EMT process, up-regulated Slug expression and enhanced the invasion, metastasis and proliferation of lung adenocarcinoma cells.Conclusions: Therefore, FBP1 can be used as one of the potential clinical targets through inhibiting glycolysis, cell invasion and proliferation by inhibiting Slug mediated EMT processes.

BackgroundEsophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a 5-year survival rate of only 20%. More than 80% of ESCC patients possess TP53 mutation, which abolishes the G1/S checkpoint and accelerates the cell cycle. Thus, WEE1 and PKMYT1, regulators of G2/M phase in cell cycle, play essential roles in TP53-mutated cancer cells. PD0166285(PD) is a pyridopyrimidine compound that can inhibit WEE1 and PKMYT1 simultaneously, however, the effects of PD on ESCC, either as monotherapy or in combination therapy with radiotherapy, remain unclear.MethodsTo measure the anti-tumor efficacy of PD in ESCC cells, cell viability, cell cycle and cell apoptosis assays were examined in KYSE150 and TE1 cells with PD treatment. The combination therapy of PD and irradiation was also performed in ESCC cells to find whether PD can sensitize ESCC cells to irradiation. Vivo assays were also performed to investigate the efficacy of PD.ResultsWe found that the IC50 values of PD among ESCC cells ranged from 234 to 694 nM, PD can regulate cell cycle and induce cell apoptosis in ESCC cells in a dose-dependent manner. When combined with irradiation, PD sensitized ESCC cells to irradiation by abolishing G2/M phase arrest, inducing a high ratio of mitosis catastrophe, eventually leading to cell death. We also demonstrated that PD can attenuate DNA damage repair by inhibiting Rad51, further research also found the interaction of WEE1 and Rad51. In vivo assays, PD inhibited the tumor growth in mice, combination therapy showed better therapeutic efficacy.ConclusionPD0166285 can exert antitumor effect by inhibiting the function of WEE1 and PKMYT1 in ESCC cells, and also sensitize ESCC cells to irradiation not only by abolishing G2/M arrest but also attenuating DNA repair directly. We believe PD0166285 can be a potent treatment option for ESCC in the future.

Esophageal squamous cell carcinoma (ESCC) has become a major health risk to human health. Although significant clinical progress has been made in the treatment of ESCC, the prognosis of patients still needs to be improved. Therefore, it is important to screen effective molecular indicators for the prognosis of ESCC. In this study, the intersection of up-regulated genes, down-regulated genes, and Wnt signaling pathway-related genes in ESCC was taken, and 47 overlapping genes were found. PRICKLE1 was determined to be an independent prognostic factor in ESCC based on univariate and multifactorial COX risk regression models. Kaplan-Meier survival curves showed that patients in the PRICKLE1 high expression group had significantly better overall survival. In addition, we performed various experiments to examine the effects of PRICKLE1 overexpression on proliferation, migration, and apoptosis of ESCC cells. The experimental results showed that the PRICKLE1-OE group had reduced cell viability, significantly lower migration ability and significantly higher apoptosis rate compared to the NC group.Therefore, we hypothesized that high PRICKLE1 expression could be used to predict the survival rate of ESCC patients, which could be used as an independent prognostic indicator for ESCC patients and provide potential applications for ESCC clinical treatment.

BackgroundFor peripheral pulmonary nodules, the regularity of lymph node (LN) metastasis has not been studied. This study aimed to evaluate the metastasis pattern of intrapulmonary and relevant mediastinal lymph nodes in early-stage lung cancer, and further selected patients who were of low risk of LN metastasis as potential population to receive sub-lobectomy.MethodsThis study prospectively included consecutive patients with peripheral clinical T1N0M0 disease who underwent complete resection with LN dissection or sampling from August 2014 to July 2015. The patients were followed up to 15, May 2021. Univariable or multivariable Logistic analysis was used to identify the risk factors. Models predicting LN metastasis risk were conducted. The area under the curve for the receiver operating characteristic curves was used to evaluate the diagnostic value. Disease-free survival and overall survival were compared between groups.ResultsFinally, 201 patients were included in this study. For patients with negative tumor-bearing (TB) 13 and 14 station LNs, the positive rate of other lymph node stations was extremely low. Maximum CT value, pleural indentation and CEA level were risk factors for N1 station LNs metastasis. Besides, the factors above and lobulation sign were risk factors for skip metastasis beyond TB 13 and 14 station LNs. We constructed two scoring tables to predict N1 station metastasis and skip metastasis beyond TB 13 and 14 station. The AUC were 0·837 and 0·823, respectively. Based on the first table, 40·9% of patients suffered N1 station LNs metastasis and 27·3% had N2 disease in “high risk group” while the proportion was only 5·7% and 4·5% in “low risk group”. For patients with negative TB13 and TB14 station LNs, based on the latter table, 11·1% of patients had N1 stations LNs metastasis and 16·7% had pN2 disease in “high risk group” while only 2·3% patients in “low risk group” suffered this kind of metastasis.ConclusionFor peripheral pulmonary nodules patients, stations 13 and 14 LNs may be the sentinel nodes. For patients with low risk of N1 metastasis and skip metastasis, sub-lobar resection might be sufficient for those who were of negative TB 13 and 14 station LNs.