Purpose: The function of curcumin on the gastric cancer cell line, SGC-7901 is unknown. The present study aimed to observe the effects of curcumin on gastric cancer cells through the Shh and Wnt signaling pathways. Methods: SGC-7901 cells were transfected with si-Gli1 and si-β-catenin siRNA, then cells were stimulated with curcumin and its effects on cell migration, invasion, cytoskeleton remodeling, EMT, apoptosis and cell cycle were investigated by transwell assays, immunofluorescence and flow cytometry assays. The interaction between Gli1 and β-catenin was observed by co-immunoprecipitation. Results: We show that curcumin suppressed the expression of Shh, Gli1 and Foxm1 in the Shh signaling pathway, and the expression of β-catenin in the Wnt signaling pathway in SGC-7901 cells, both in mRNA and protein. As a result, cellular migration, invasion and cytoskeletal remodeling ability decreased. Our results revealed that when stimulated with curcumin, cells showed decreased cellular migration and invasion, while enhanced apoptosis. In addition, curcumin induced cytoskeletal remodeling and S phase cell cycle arrest. The inhibition of Shh and Wnt signaling pathway and the addition of curcumin also inhibited the epithelial–mesenchymal transition process. Furthermore, a physical interaction was observed between Gli1 of the Shh signaling and β-catenin of the Wnt signaling in these cells, but curcumin inhibited the interaction of these two proteins. Conclusion: The present study indicated that curcumin plays an anti-tumor role through Gli1-β-catenin pathway in gastric cancer SGC-7901 cells.

Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling plays a crucial role in anterior–posterior (A–P) axial patterning of vertebrate embryos by promoting posterior development. In our screens for novel developmental regulators in Xenopus embryos, we identified Fam3b as a secreted factor regulated in ectodermal explants. Family with sequence similarity 3 member B (FAM3B)/PANDER (pancreatic-derived factor) is a cytokine involved in glucose metabolism, type 2 diabetes, and cancer in mammals. However, the molecular mechanism of FAM3B action in these processes remains poorly understood, largely because its receptor is still unidentified. Here we uncover an unexpected role of FAM3B acting as a FGF receptor (FGFR) ligand in Xenopus embryos. fam3b messenger RNA (mRNA) is initially expressed maternally and uniformly in the early Xenopus embryo and then in the epidermis at neurula stages. Overexpression of Xenopus fam3b mRNA inhibited cephalic structures and induced ectopic tail-like structures. Recombinant human FAM3B protein was purified readily from transfected tissue culture cells and, when injected into the blastocoele cavity, also caused outgrowth of tail-like structures at the expense of anterior structures, indicating FGF-like activity. Depletion of fam3b by specific antisense morpholino oligonucleotides in Xenopus resulted in macrocephaly in tailbud tadpoles, rescuable by FAM3B protein. Mechanistically, FAM3B protein bound to FGFR and activated the downstream ERK signaling in an FGFR-dependent manner. In Xenopus embryos, FGFR activity was required epistatically downstream of Fam3b to mediate its promotion of posterior cell fates. Our findings define a FAM3B/FGFR/ERK-signaling pathway that is required for axial patterning in Xenopus embryos and may provide molecular insights into FAM3B-associated human diseases. Significance How distinct body regions form along the anterior–posterior axis in vertebrate embryos is a fascinating and incompletely understood developmental process. FAM3B/PANDER is a secreted protein involved in glucose metabolism and type 2 diabetes pathogenesis in mammals, but its receptor has been unknown. Here, we report that FAM3B binds to transmembrane fibroblast growth factor receptors (FGFRs) and activates their downstream signaling pathway. In frog embryos, gain-of-function of FAM3B impairs head development and induces ectopic tail-like structures, whereas loss-of-function of FAM3B promotes head development. FGFR is required downstream of FAM3B for head-to-tail patterning. Our results reveal that FAM3B functions by activating the FGFR pathway in frog embryos and mammalian cells and shed light on its possible role in human diseases.

Triple‑negative breast cancer (TNBC) is highly invasive, has a high rate of recurrence and is associated with a poor clinical outcome when compared with non‑TNBC due to a lack of effective and targeted treatments. The coatomer protein complex subunit β2 (COPB2) is upregulated in various types of malignant cancer. The present study demonstrated that COPB2 expression levels were significantly upregulated in breast carcinoma HS‑578T cells (clonal cells originating from TNBC) when compared with non‑TNBC MCF‑7 cells. HS‑578T cells also exhibited higher rates of proliferation, invasion and transendothelial migration when compared with MCF‑7 cells. Moreover, it was identified that genetically silencing the COPB2 gene using a lentivirus‑short hairpin RNA inhibited the proliferative, colony formation, migratory and invasive properties of the TNBC HS‑578T cells. Mediation of the COPB2 silencing effect may be associated with regulating the phosphorylation of serine/threonine kinase AKT in the PI3K/AKT signaling pathway. These results suggested the importance of COPB2 in promoting the proliferation of TNBC cells and identified COPB2 as a potential novel therapeutic target.