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Early metastasis of pancreatic cancer (PC) leads to high mortality, and the underlying mechanism of metastasis remains unclear. Tumor necrosis factor superfamily member 9 (TNFSF9) is associated with poor prognosis in PC. Here, we investigated the effect of TNFSF9 on PC proliferation and apoptosis, and focused on the effect of TNFSF9 on PC metastasis and its potential mechanism. We found that TNFSF9 promotes PC metastasis in vivo and in vitro, and may be partially dependent on the Wnt/Snail signaling pathway. In addition, TNFSF9 also regulates the release of cytokines IL-10 and transforming growth factor-β (TGF-β) in pancreatic cancer cells through Wnt signaling to induce the M2 polarization of macrophages and promote the migration of PC cells. Overall, our study found that TNFSF9 may directly promote PC metastasis or indirectly promote PC metastasis through macrophage M2 polarization. Our study provides a new costimulatory target for the treatment of PC.

As an important transcription factor, zinc-finger and BTB domain-containing 7B (ZBTB7C) plays an important role in a variety of tumors. However, its relationship with human immunity is unclear. This article aims to study its differential expression and survival across cancers and explore the relationships between its differential expression and the tumor microenvironment and immune cell infiltration. In this study, we used R software to process The Cancer Genome Atlas (TCGA) data and explored the expression pattern and prognostic value of ZBTB7C across cancers. Next, we comprehensively explained the important role of ZBTB7C in several tumor types in terms of tumor mutational burden (TMB), microsatellite instability (MSI) and immune cell infiltration. In general, the expression level of ZBTB7C in tumor tissues was lower than that in normal tissues. Highly expressed ZBTB7C was beneficial to the survival of patients with colon adenocarcinoma (COAD), lymphoid neoplasm diffuses large B cell lymphoma (DLBC), esophageal carcinoma (ESCA) and mesothelioma (MESO). Multivariate analysis showed that the expression of ZBTB7C was an independent prognostic factor in COAD and MESO. In COAD, the expression of ZBTB7C was positively correlated with both TMB and MSI. In colorectal cancer (CRC), there was a significant positive correlation between ZBTB7C expression and immune cell infiltration, especially the infiltration of mast cells and B cells. In conclusion, ZBTB7C can be used as a potential therapeutic target across cancers and is related to immune cell infiltration.

Downregulation of Carnitine palmitoyltransferase-2 (CPT2) has been shown to be highly associated with the progression of several cancers, but little known about its expression, biological functions and mechanisms in colorectal cancer (CRC).Bioinformatics analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets was used to explore the expression of CPT2, the relationship between CPT2 expression and clinicopathologic features, as well as the overall survival of CRC. Cox's proportional hazards regression model was used to analyze independent prognostic factors of CRC. In vitro, CRC tissues were analyzed by RT-qPCR, IHC, IF and western blotting to verify CPT2 expression. Colony formation, CCK-8, cell cycle, apoptosis, transwell and wound healing assays were performed to examine the functions of CPT2 in CRC. In vivo, nude mouse xenograft experiment was used to further examine the effect of CPT2 on tumorigenesis. Furthermore, gene set enrichment analysis (GSEA) was conducted to explore the downstream pathway of CPT2. The regulation of p53 pathway by CPT2 was verified by RT-qPCR and Western blotting.CPT2 expression was frequently downregulated in CRC and correlated with poor prognosis. Low CPT2 expression was significantly associated with age, lymph node metastasis, distant metastasis and TMN stage. Univariate and multivariate analysis indicated that low CPT2 expression was an independent prognostic factor for poorer overall survival. Functionally, overexpression of CPT2 in CRC cells induced growth suppression, cell cycle arrest at the G1 phase, enhanced apoptosis and reduced cell migration and invasion. Conversely, knockdown of CPT2 contributed to cell proliferation, migration and invasion, increased the proportion of S phase cells, decreased the proportion of G1 phase cells and inhibited apoptosis. Mechanistically, we found that CPT2 overexpression can increase p53 expression by activating p-p53, leading to p21, Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP activation and Bcl2, MDM2 deactivation, thereby inhibiting tumor proliferation and promoting apoptosis. CPT2 knockdown yielded opposite results.These findings suggest that CPT2 may be a novel prognostic marker of CRC and downregulation of CPT2 can promote proliferation and inhibit apoptosis through p53 pathway in CRC. Strategies targeting CPT2 may be developed as therapies for CRC.

The effect of tumor necrosis factor superfamily member 9 (TNFSF9) on the metastasis of pancreatic cancer (PC) and the underlying mechanism remain unclear. We studied the expression of TNFSF9 in pancreatic cancer and its relationship with immune cells. We further explored the effect of TNFSF9 on pancreatic cancer metastasis by inducing macrophage polarization, and evaluated the expression of Src/FAK/p-Akt/IL-1β signals in macrophages after knocking down TNFSF9. The data shows that TNFSF9 expression is elevated in pancreatic cancer and is related to the poor prognosis of patients with pancreatic cancer. In addition, TNFSF9 may induce the M2 polarization of macrophages through Src/FAK/p-Akt/IL-1β signals, thereby promoting the migration of pancreatic cancer cells. In conclusion, our data reveals that TNFSF9 may become a predictive biomarker of pancreatic cancer and provides a new intervention target for the immunotherapy of pancreatic cancer.

The cellular environment impacts a myriad of cellular functions by providing signals that can modulate cell phenotype and function. Physical cues such as topography, roughness, gradients, and elasticity are of particular importance. Thus, synthetic substrates can be potentially useful tools for exploring the influence of the aforementioned physical properties on cellular function. Many micro- and nanofabrication processes have been employed to control substrate characteristics in both 2D and 3D environments. This review highlights strategies for modulating the physical properties of surfaces, the influence of these changes on cell responses, and the promise and limitations of these surfaces in in-vitro settings. While both hard and soft materials are discussed, emphasis is placed on soft substrates. Moreover, methods for creating synthetic substrates for cell studies, substrate properties, and impact of substrate properties on cell behavior are the main focus of this review.