NPLOC4 is a potential target and a poor prognostic signature in lung squamous cell carcinoma.

Few prognostic biomarkers exist for lung squamous cell carcinoma (LUSC), which has a poor five-year survival rate. Using bioinformatics, this study evaluated NPLOC4 as a prognostic marker for patients with lung squamous cell carcinoma. Shorter survival periods and tumor growth were linked to high NPLOC4 expression.Disulfiram (DSF) combined with copper (Cu) targets NPLOC4 to achieve antitumor effects in lung squamous cell carcinoma. Thus, we investigated the effects of DSF with Cu in LUSC. Gene-set enrichment analysis identified ubiquitin-mediated proteolysis as the NPLOC4-associated mechanism influencing LUSC prognosis. In SK-MES-1 cell lines, DSF + Cu increased K48-linked ubiquitinated protein expression and apoptosis. This study identified NPLOC4 as a prognostic biomarker and a potential therapeutic target for LUSC.

Current status and prospects of GREM1 research in cancer (Review).

GREM1 is a secreted protein that antagonizes bone morphogenetic proteins (BMPs) and participates in critical biological processes, including embryonic development, organogenesis and tissue differentiation. Gremlin 1 (GREM1) is also an inhibitor of TGF-ß and a ligand for vascular endothelial growth factor receptor 2. In addition, GREM1 can induce cells, participate in the process of epithelial-mesenchymal transition, and then participate in tumor development. GREM1 has a variety of biological functions and can participate in the malignant progression of a variety of tumors through the BMP signaling pathway. GREM1 also can inhibit TGF-ß in some tumors, thereby inhibiting tumors, and its involvement in tumor development varies in different types of cancer. The present review examines the role and function of GREM1 in tumors. GREM1 is expressed in a variety of tumor types. GREM1 expression can affect the epithelial-mesenchymal transformation of tumor cells. GREM1 has been studied in breast and colon cancer, and its potential role is to promote cancer. However, in pancreatic cancer, which was found to act differently from other cancer types, overexpression of GREM1 inhibits tumor metastasis. The present review suggests that GREM1 can be a diagnostic and prognostic indicator. In future studies, the study of GREM1 based on single-cell sequencing technology will further clarify its role and function in tumors.

Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways.

Disulfiram (DSF) is an anti-alcoholism medication with superior antitumor activity and clinical safety; its antitumor mechanisms in gastric cancer (GC) have not been fully explored. In the present work, low nontoxic concentrations of copper (Cu) ions substantially enhanced DSF's antitumor activity, inhibiting the proliferation and growth of GC cell lines. DSF/Cu elevated the generation of reactive oxygen species (ROS), and apoptosis was induced in an ROS-dependent manner. This process might involve primary inhibition GC by DSF/Cu through induction of apoptosis via the ROS/mitogen-activated protein kinase pathway. Disordering transportation of ubiquitinated protein may also fuel the process. In summary, we found that DSF exerts antitumor effects on GC. DSF/Cu should be considered as adjunctive therapy for GC.