The dual role of SUSD2 in cancer development.

Sushi domain-containing protein 2 (SUSD2, also known as the complement control protein domain) is a representative and vital protein in the SUSD protein family involved in many physiological and pathological processes beyond complement regulation. Cancer is one of the leading causes of death worldwide. The complex role of SUSD2 in tumorigenesis and cancer progression has raised increasing concerns. Studies suggest that SUSD2 has different regulatory tendencies among different tumors and exerts its biological effects in a cancer type-specific manner; for instance, it has oncogenic effects on breast cancer, gastric cancer, and glioma and has tumor-suppression effects on lung cancer, bladder cancer, and colon cancer. Moreover, SUSD2 can be regulated by noncoding RNAs, its promoter methylation and other molecules, such as Galectin-1 (Gal-1), tropomyosin alpha-4 chain (TPM4), and p63. The therapeutic implications of targeting SUSD2 have already been preliminarily revealed in some malignancies, including melanoma, colon cancer, and breast cancer. This article reviews the role and regulatory mechanisms of SUSD2 in cancer development, as well as its structure and distribution. We hope that this review will advance the understanding of SUSD2 as a diagnostic and/or prognostic biomarker and provide new avenues for the development of novel cancer therapies.

FBXO32-mediated degradation of PTEN promotes lung adenocarcinoma progression.

FBXO32, a member of the F-box protein family, is known to play both oncogenic and tumor-suppressive roles in different cancers. However, the functions and the molecular mechanisms regulated by FBXO32 in lung adenocarcinoma (LUAD) remain unclear. Here, we report that FBXO32 is overexpressed in LUAD compared with normal lung tissues, and high expression of FBXO32 correlates with poor prognosis in LUAD patients. Firstly, we observed with a series of functional experiments that FBXO32 alters the cell cycle and promotes the invasion and metastasis of LUAD cells. We further corroborate our findings using in vivo mouse models of metastasis and confirmed that FBXO32 positively regulates LUAD tumor metastasis. Using a proteomic-based approach combined with computational analyses, we found a positive correlation between FBXO32 and the PI3K/AKT/mTOR pathway, and identified PTEN as a FBXO32 interactor. More important, FBXO32 binds PTEN via its C-terminal substrate binding domain and we also validated PTEN as a bona fide FBXO32 substrate. Finally, we demonstrated that FBXO32 promotes EMT and regulates the cell cycle by targeting PTEN for proteasomal-dependent degradation. In summary, our study highlights the role of FBXO32 in promoting the PI3K/AKT/mTOR pathway via PTEN degradation, thereby fostering lung adenocarcinoma progression.

Reversal Effect of Phosphorus on Catalytic Performances of Supported Nickel Catalysts in Reductive Amination of 1,6-Hexanediol.

The reductive amination of 1,6-hexanediol with ammonia is one of the most promising green routes for synthesis of 1,6-hexanediamine. Herein, we developed a phosphorous modified Ni catalyst of Ni-P/Al2O3. It presented satisfactory improved selectivity to 1,6-hexanediamine in the reductive amination of 1,6-hexanediol compared to the Ni/Al2O3 catalyst. The phosphorous tended to interact with Al2O3 to form AlPOx species, induced Ni nanoparticle to be flatter, and the decrease of strong acid sites, the new-formed Ni-AlPOx-Al2O3 interface and the flatter Ni nanoparticle were the key to switch the dominating product from hexamethyleneimine to 1,6-hexanediamine. This work develops an efficient catalyst for production of 1,6-hexanediamine from the reductive amination of 1,6-hexanediol, and provides a point of view about designing selective non-noble metal catalysts for producing primary diamines via reductive amination of diols.

VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk.

Triple-negative breast cancer (TNBC) has long been considered a major clinical challenge due to its aggressive behavior and poor prognosis. Cancer stem cells (CSCs) are known as the main cells responsible for tumor origination, progression, recurrence and metastasis. Here, we report that M2-type tumor-associated macrophages (TAMs) contribute to cancer stemness in TNBC cells via the secretion of VEGFA. Reciprocally, elevated VEGFA expression by TAM-educated TNBC cells acts as a regulator of macrophage polarization, therefore constitute a feed-back loop between TNBC cells and TAMs. Mechanistically, VEGFA facilitates the CSC phenotype via the NRP-1 receptor and downstream GAPVD1/Wnt/ß-catenin signaling pathway in TNBC cells. Our study underscores the crosstalk between TNBC cells and TAMs mediated by VEGFA and further clarifies the role and underlying mechanisms of the VEGFA/NRP-1/GAPVD1 axis in regulating cancer stemness. We also document an immunosuppressive function of VEGFA in the tumor microenvironment (TME). Therefore, the present study indicates crosstalk between TNBC cells and TAMs induced by VEGFA and provides a potential implication for the combination of immunotherapy and VEGFA-targeted agents in TNBC therapy.

Comprehensive analysis of the prognostic value and immune infiltration of FGFR family members in gastric cancer.

Background: Fibroblast growth factor receptors (FGFRs) modulate numerous cellular processes in tumor cells and tumor microenvironment. However, the effect of FGFRs on tumor prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains controversial. Methods: The expression of four different types of FGFRs was analyzed via GEPIA, TCGA-STAD, and GTEX databases and our 27 pairs of GC tumor samples and the adjacent normal tissue. Furthermore, the Kaplan-Meier plot and the TCGA database were utilized to assess the association of FGFRs with clinical prognosis. The R software was used to evaluate FGFRs co-expression genes with GO/KEGG Pathway Enrichment Analysis. In vitro and in vivo functional analyses and immunoblotting were performed to verify FGFR4 overexpression consequence. Moreover, the correlation between FGFRs and cancer immune infiltrates was analyzed by TIMER and TCGA databases. And the efficacy of anti-PD-1 mAb treatment was examined in NOG mouse models with overexpressed FGFR1 or FGFR4. Results: The expression of FGFRs was considerably elevated in STAD than in the normal gastric tissues and was significantly correlated with poor OS and PFS. ROC curve showed the accuracy of the FGFRs in tumor diagnosis, among which FGFR4 had the highest ROC value. Besides, univariate and multivariate analysis revealed that FGFR4 was an independent prognostic factor for GC patients. According to a GO/KEGG analysis, the FGFRs were implicated in the ERK/MAPK, PI3K-AKT and extracellular matrix (ECM) receptor signaling pathways. In vivo and in vitro studies revealed that overexpression of FGFR4 stimulated GC cell proliferation, invasion, and migration. In addition, FGFR1 expression was positively correlated with infiltrating levels of CD8+ T-cells, CD4+ T-cells, macrophages, and dendritic cells in STAD. In contrast, FGFR4 expression was negatively correlated with tumor-infiltrating lymphocytes. Interestingly, overexpression of FGFR1 in the NOG mouse model improved the immunotherapeutic impact of GC, while overexpression of FGFR4 impaired the effect. When combined with an FGFR4 inhibitor, the anti-tumor effect of anti-PD-1 treatment increased significantly in a GC xenograft mouse model with overexpressed FGFR4. Conclusions: FGFRs has critical function in GC and associated with immune cell infiltration, which might be a potential prognosis biomarker and predictor of response to immunotherapy in GC.

LHPP suppresses colorectal cancer cell migration and invasion in vitro and in vivo by inhibiting Smad3 phosphorylation in the TGF-ß pathway.

The roles of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) in tumorigenesis have been recently proven in hepatocellular carcinoma (HCC), cervical, pancreatic, bladder, and thyroid cancers. Previous research demonstrated that LHPP repressed cell proliferation and growth by inactivating the phosphatidylinositol 3-kinase/AKT signaling pathway in vitro and in vivo. However, the functions and potential mechanisms of LHPP as a tumor suppressor in colorectal cancer (CRC) metastasis are still unknown. Consequently, the Transwell assay and xenograft nude model showed that LHPP inhibited migration and invasion of CRC cells in vitro and in vivo, respectively. The expression of total and nuclear epithelial-to-mesenchymal transition (EMT)-related proteins were significantly reduced after LHPP upregulation. Human Gene Expression Array and IPA (Ingenuity Pathway Analysis) commercial software were applied to identify differentially expressed genes (DEGs) and potential cell signaling pathways. A total of 330 different genes were observed, including 177 upregulated genes and 153 downregulated genes. Bioinformatics analysis suggested that the transforming growth factor-ß (TGF-ß) signaling pathway was highly inactivated in this study. Then, Smad3 phosphorylation was apparently decreased, whereas Smad7 expression was markedly enhanced after upregulating LHPP expression. These results were proven once again after TGF-ß1 stimulation. Furthermore, a specific inhibitor of Smad3 phosphorylation (SIS3) was applied to verify that LHPP repressed EMT of cancer cells by attenuating TGF-ß/Smad signaling. The results suggested that suppression of the TGF-ß/Smad signaling pathway by LHPP overexpression could be abolished by SIS3.

Identification of core genes and clinical outcomes in tumors originated from endoderm (gastric cancer and lung carcinoma) via bioinformatics analysis.

ABSTRACT: During last decade, bioinformatics analysis has provided an effective way to study the relationship between various genes and biological processes. In this study, we aimed to identify potential core candidate genes and underlying mechanisms of progression of lung and gastric carcinomas which both originated from endoderm. The expression profiles, GSE54129 (gastric carcinoma) and GSE27262 (lung carcinoma), were collected from GEO database. One hundred eleven patients with gastric carcinoma and 21 health people were included in this research. Meanwhile, there were 25 lung carcinoma patients. Then, 75 differentially expressed genes were selected via GEO2R online tool and Venn software, including 31 up-regulated genes and 44 down-regulated genes. Next, we used Database for Annotation, Visualization, and Integrated Discovery and Metascpe software to analyze Kyoto Encyclopedia of Gene and Genome pathway and gene ontology. Furthermore, Cytoscape software and MCODE App were performed to construct complex of these differentially expressed genes . Twenty core genes were identified, which mainly enriched in extracellular matrix-receptor interaction, focal adhesion, and PI3K-Akt pathway (P < .01). Finally, the significant difference of gene expression between cancer tissues and normal tissues in both lung and gastric carcinomas was examined by Gene Expression Profiling Interactive Analysis database. Twelve candidate genes with positive statistical significance (P < .01), COMP CTHRC1 COL1A1 SPP1 COL11A1 COL10A1 CXCL13 CLDN3 CLDN1 matrix metalloproteinases 7 ADAM12 PLAU, were picked out to further analysis. The Kaplan-Meier plotter website was applied to examine relationship among these genes and clinical outcomes. We found 4 genes (ADAM12, SPP1, COL1A1, COL11A1) were significantly associated with poor prognosis in both lung and gastric carcinoma patients (P  < .05). In conclusion, these candidate genes may be potential therapeutic targets for cancer treatment.

Laparoscopic Duodenal Switch Versus Roux-en-Y Gastric Bypass at a High-Volume Community Hospital: a Retrospective Cohort Study from a Rural Setting.

BACKGROUND: The classic duodenal switch (DS) represents a minority of bariatric procedures due to its high complexity and potential for complications. METHODS: A retrospective chart review was conducted on 100 laparoscopic DS cases from 2014 to 2018 at an accredited program in a rural community hospital and compared to 100 laparoscopic Roux-en-Y gastric bypasses (RYGB). Primary outcomes were 30-day morbidity and mortality. Secondary outcomes included anastomotic leak and remission of type 2 diabetes. RESULTS: There were more demographic risk factors for DS. The 30-day morbidity was higher for DS compared to RYGB (31% vs 13%, respectively; p = 0.0037). There was one mortality for DS and none for RYGB. There were statistically significant longer intraoperative times, greater EBL, and greater decrease in BMI for DS. The DS had a lower incidence of anastomotic ulcers (4% vs 13%, respectively; p = 0.0289), with a higher incidence of subsequent surgery beyond 30 days (21% vs 8%, respectively; p = 0.0160). There were 3 anastomotic leaks for DS and none for RYGB, although not statistically significant (p = 0.2463). The DS was more likely to eradicate hypertension, but the RYGB was more likely to eradicate GERD. There were no statistically significant differences for type 2 diabetes remission (92.1% vs 89.5%, respectively; p = 0.7239). CONCLUSION: Laparoscopic DS offers greater weight loss and hypertension remission, with lower incidence of anastomotic ulcers, but at the expense of greater morbidity and need for subsequent surgery, with no significant differences in type 2 diabetes remission when compared to RYGB in a rural community hospital program.

Olfactory and visual responses of the longlegged chafer Hoplia spectabilis Medvedev (Coleoptera: Scarabaeidae) in Qinghai Province, China.

BACKGROUND: Monitoring traps and control methods are needed for the long-legged chafer, Hoplia spectabilis Medvedev, which has recently reached outbreak numbers in pastureland of Qinghai Province, China. RESULTS: Field trapping experiments, using cross-pane funnel (barrier) traps, showed that H. spectabilis adults were not significantly attracted to branches of the host plant Dasiphora fructicosa (L.) Rydb. However, beetles were slightly attracted to similar host plant branches infested by conspecific beetles, possibly owing to weakly attractive volatiles, primarily (Z)-3-hexenyl acetate, released from beetle-damaged host leaves. This compound was weakly attractive when released from traps. However, H. spectabilis beetles showed strong visual responses to yellow- or white-painted trap panes, with weaker responses to blue, red or green panes, and least response to black panes. Black traps at 0.2-1.5 m above ground intercepted significantly more beetles than traps at 2.5 m. The mean flight height based on trap catches was 0.88 m (SD = 0.76), yielding an effective flight layer of 1.9 m. Flight response of beetles to colored barrier traps occurred between 10:00 and 18:00, and peaked between 12:00-14:00, when daily temperatures reached their maximum. CONCLUSION: Unbaited yellow or white cross-pane funnel traps are recommended for both monitoring and mass-trapping programs against this economically and ecologically important scarab beetle.