Research progress on BTG2 in non-tumor diseases (Review)

Research and advances in TK1-mediated metabolic reprogramming in modulating the tumor immune microenvironment in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is still one of the leading causes of cancer-related deaths in the world. It is characterized by significant metabolic disorders and immunosuppressive tumor microenvironment(TME). As a key enzyme in the thymidine remedy pathway, TK1 is traditionally regarded as a biomarker related to proliferation. However, recent evidence shows that the biological function of TK1 has gone beyond the category of nucleotide metabolism and may be involved in a variety of processes related to tumor progression. In this review, we summarize the current understanding of the biological function of TK1 and discuss its evolving role in HCC. Let's first examine the classical and non-classical functions of TK1, including its participation in nucleotide homeosism, metabolic adaptation and tumor-related signal networks. Then, we reviewed the recent evidence that TK1 promotes metabolic reprogramming by regulating glycolysis, nucleotide metabolism and a wider range of metabolic signaling pathways. In addition, we discussed how TK1-related metabolic changes can affect the tumor immune microenvironment(TIME) by promoting nutritional competition, lactic acid accumulation, and establishing an immunosuppressive microenvironment involving CD8 + T cells, tumor-related macrophages, regulatory T cells, medullary inhibitory cells and dendritic cells. Importantly, more and more data support the view that TK1 acts as a key node in connecting metabolic reprogramming and immune remodeling in HCC. Collectively, this review proposes a conceptual framework in which TK1 is viewed not merely as a proliferation marker but as a potential regulator of the metabolic–immune ecosystem in HCC. A deeper understanding of TK1-mediated metabolic and immunological interactions may facilitate the development of novel biomarkers and precision therapeutic strategies for patients with HCC.

Glycoprotein nonmetastatic B as a pharmacological target in cancer: structural mechanisms, druggability, and therapeutic translation.

The malignant progression of cancer depends not only on oncogenic driver mutations but also on the adaptive rewiring of organelle stress responses that sustain cell survival under hostile tumor microenvironment (TME) conditions. Among these, the hijacking of lysosomal homeostasis has emerged as a critical vulnerability and a driver of therapeutic resistance. Glycoprotein nonmetastatic B (GPNMB), a highly glycosylated type I transmembrane protein predominantly localized to lysosomes, is robustly upregulated across multiple cancer types as an adaptive responder to lysosomal stress. In tumors, GPNMB drives proliferation, metastasis, and immune evasion by engaging multiple oncogenic signaling cascades, while simultaneously shaping an immunosuppressive TME through CD8+ T cell exhaustion and cytokine networks. Clinically, high GPNMB expression correlates with poor prognosis in breast cancer, hepatocellular carcinoma (HCC), lung cancer, glioblastoma (GBM), gastric cancer (GC), and osteosarcoma (OS), positioning it as both a prognostic biomarker and a therapeutic target. The GPNMB-directed antibody-drug conjugate (ADC) glembatumumab vedotin (GV) has demonstrated clinical activity in triple-negative breast cancer (TNBC) and melanoma, yet its efficacy remains constrained by target expression heterogeneity, the reliance on lysosomal trafficking for payload release, and dose-limiting toxicities. Emerging strategies, including bispecific antibodies, immunotoxins, and senolytic elimination of GPNMB-high damaged cells, are expanding the therapeutic landscape. This review dissects the molecular mechanisms, pathological roles, and evolving clinical applications of GPNMB in cancer, highlighting current challenges and future directions for precision oncology.

The PDPK1-RSK2 axis as a potential convergent therapeutic vulnerability in B-cell lymphomas.

INTRODUCTION B-cell lymphomas (BCLs) are the most prevalent group of hematologic cancers, encompassing various subtypes, each with a distinct clinical course shaped by cell of origin, genetics, and etiology. Recent advances in subtype-specific immunochemotherapy, targeted therapies, and cellular immunotherapy have improved outcomes for BCLs; nonetheless, some cases remain resistant to existing treatments. To address these resistant disease states, especially across multiple subtypes, the development of new universal targeted therapies could be transformative. AREAS COVERED This review first highlights what distinguishes the PDPK1/RSK2 signaling axis, outlines its normal biological functions, and briefly examines its roles in solid tumors. It then narrows the focus to BCLs, supported by evidence from our research on pathway activation, functional dependence, prognostic value, and early-stage drug development. EXPERT OPINION The PDPK1/RSK2 axis is activated in nearly all BCL subtypes and likely plays a significant role in disease development. This suggests the potential for treatments that work across subtypes, despite their genetic and phenotypic differences. Targeting a shared signaling pathway might help overcome resistance seen with traditional precision medicine and support the development of new therapies for rare disease subtypes. However, because current research remains preclinical, more work is necessary.

THBS2: the key hub linking breast cancer stroma, immunity, and therapeutic response

PSMA6 drives non-small cell lung cancer progression by stabilizing NEDD8 and activating NF-κB signaling

Background Non‑small cell lung cancer (NSCLC) is a major cause of cancer‑associated death globally. Elucidating novel molecular drivers is essential for targeted therapy development. This study sought to investigate the function and regulatory mechanism of proteasome 20S subunit alpha 6 (PSMA6) in NSCLC. Methods Proteasome 20S subunit alpha 6 (PSMA6) expression in NSCLC tissues and cells was analyzed using The Cancer Genome Atlas (TCGA) datasets, immunohistochemistry, and Western blotting. Gain- and loss-of-function assays were performed to evaluate its biological functions. Protein interaction assays and functional rescue experiments were conducted to investigate the underlying mechanisms. Results We found that PSMA6 was significantly upregulated in NSCLC tissues and cell lines and was associated with poor patient prognosis. Functional experiments demonstrated that PSMA6 promoted NSCLC cell proliferation and migration. Mechanistically, PSMA6 activated nuclear factor kappa B (NF-κB) signaling by enhancing p65 nuclear translocation and IκBα phosphorylation. Further investigation revealed that PSMA6 directly interacted with neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) and increased its protein stability without affecting its mRNA level. Importantly, NEDD8 knockdown abolished PSMA6-induced NF-κB activation and malignant phenotypes, confirming that PSMA6 exerts its oncogenic effects through the NEDD8/NF-κB axis. Conclusions Our findings identify a novel PSMA6/NEDD8/NF-κB regulatory axis that promotes NSCLC progression and suggest PSMA6 as a potential therapeutic target.

Exploring the therapeutic potential of NCX1 in hematological cancers; integration of molecular docking, bioinformatics approaches, and experimental validation.

Findings have demonstrated NCX1 as a biologically informative marker of myeloid differentiation and a promising therapeutic weak point within calcium signaling networks in hematological malignancies, providing a rationale for future functional and single-cell validation studies.