Biochimica et biophysica acta. Reviews on cancer最新文献

RNF43 and ZNRF3 are recognized as important regulators of Wnt/β-catenin signaling by maintaining Wnt-receptors at minimal essential levels. In various cancer types, particularly gastrointestinal tumors, mutations in these genes lead to abnormal Wnt-dependent activation of β-catenin signaling. However, recent findings implicate RNF43/ZNRF3 also in the regulation of other tumor-related proteins, including EGFR, BRAF, and the BMP-signaling pathway, which may have important implications for tumor biology. Additionally, we describe in detail how phosphorylation and ubiquitination may finetune RNF43 and ZNRF3 activity. We also address the variety of mutations observed in cancers and the mechanism through which they support tumor growth, and challenge the prevailing view that specific missense mutations in the R-spondin and RING domains may possess dominant-negative activity in contributing to tumor formation.

Numerous studies have demonstrated the importance of the Epstein-Barr Virus (EBV), which was initially identified in 1964 while studying Burkitt's lymphoma, in the development of a number of cancers, including nasopharyngeal carcinoma, Hodgkin's lymphoma, Burkitt's lymphoma, and EBV-associated gastric carcinoma. Gammaherpesvirus EBV is extremely common; by adulthood, over 90 % of people worldwide have been infected. Usually, the virus causes a permanent latent infection in B cells, epithelial cells, and NK/T cells. It then contributes to oncogenesis by inhibiting apoptosis and promoting unchecked cell proliferation through its latent proteins, which include EBNA-1, LMP1, and LMP2A. Tumor progression further accelerated by EBV's capacity to transition between latent and lytic phases, especially in cases of nasopharyngeal carcinoma. Although our understanding of the molecular underpinnings of EBV has advanced, there are still difficulties in identifying latent infections and creating targeted therapeutics. To tackle EBV-associated malignancies, current research efforts are concentrated on developing vaccines, developing better diagnostic tools, and developing targeted treatments. In order to improve treatment approaches and lower the incidence of EBV-related cancers worldwide, more research into the relationship between EBV and immune evasion and cancer formation is necessary.

The emergence of immunotherapies such as immune checkpoint blockade (ICB) has markedly enhanced cancer treatment outcomes for numerous patients. Nevertheless, the effectiveness of immunotherapy demonstrates substantial variation across different cancer types and individual patients. The immunosuppressive characteristics of the tumor microenvironment (TME) play a crucial role in contributing to this variation. Typically, people focus on cells with immunosuppressive functions in the TME, such as tumor-associated macrophages (TAMs), but research on TAMs alone cannot fully explain the complex structure and composition of the TME. Recent studies have reported that tumors can induce erythroid progenitor cells (EPCs) to exert immunosuppressive functions, not only acting within the TME but also secreting artemin in the spleen to promote tumor progression. In this review, we summarize the recent research on EPCs and tumors in recent years. We elucidate the mechanisms by which EPCs exert immunosuppressive functions in tumor-bearing conditions. In this review, we further propose potential therapeutic strategies targeting EPCs and emphasize the importance of in-depth exploration of the mechanisms by which EPCs regulate tumors and the immune system, as well as the significant clinical value of developing corresponding drugs.

This review explores the complex relationship between epigenetic mechanisms and Transforming Growth Factor-beta (TGF-β) signalling pathways in the field of cancer research. The study provides an overview of the latest advancements in understanding the crucial functions of epigenetic alterations, such as DNA methylation, histone modifications, and chromatin remodeling, in significantly impacting the TGF-β signalling pathway. The dynamic epigenetic modifications are essential in determining the behaviour of cancer cells, impacting the interactions with the tumor microenvironment, and affecting the overall process of carcinogenesis. Significant attention is given to Breast cancer, Lung cancer, Liver cancer, Prostate cancer, and Pancreatic cancer. Research has revealed intricate regulatory networks in these cancers, involving long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and histone post-translational modifications. These networks are closely connected to TGF-β signalling. Both findings highlight the significant interaction between epigenetic regulation and TGF-β signalling in cancer. They provide valuable insights that can guide the development of new treatment approaches to target both pathways and prevent cancer growth and metastasis.

Heterogeneous cancers that lack strong driver mutations with high penetrance, such as head and neck squamous cell carcinoma (HNSCC), present unique challenges to understanding their aetiology due to the complex interactions between genetics and environmental factors. The interplay between lifestyle factors (such as poor oral hygiene, smoking, or alcohol consumption), the oral and gut microbiome, and host genetics appears particularly important in the context of HNSCC. The complex interplay between the gut microbiota and cancer treatment outcomes has also received increasing attention in recent years. This review article describes the bidirectional communication between the host and the oral/gut microbiome, focusing on microbiome-derived metabolites and their impact on systemic immune responses and the modulation of the tumour microenvironment. In addition, we review the role of host lifestyle factors in shaping the composition of the oral/gut microbiota and its impact on cancer progression and therapy. Overall, this review highlights the rationality of considering the oral/gut microbiota as a critical determinant of cancer therapy outcomes and points to therapeutic opportunities offered by targeting the oral/gut microbiota in the management of HNSCC.

Tumor recurrence is a mechanism triggered in sparse populations of cancer cells that usually remain in a quiescent state after strict stress and/or therapeutic factors, which is affected by a variety of autocrine and microenvironmental cues. Despite thorough investigations, the biology of dormant and/or cancer stem cells is still not fully elucidated, as for the mechanisms of their reawakening, while only the major molecular patterns driving the relapse process have been identified to date. These molecular patterns profoundly interfere with the elements of cellular proteostasis systems that support the efficiency of the recurrence process. As a major proteostasis machinery, we review the role of the ubiquitin-proteasome system (UPS) in tumor cell dormancy and reawakening, devoting particular attention to the functions of its components, E3 ligases, deubiquitinating enzymes and proteasomes in cancer recurrence. We demonstrate how UPS components functionally or mechanistically interact with the pivotal proteins implicated in the recurrence program and reveal that modulators of the UPS hold promise to become an efficient adjuvant therapy for eradicating refractory tumor cells to impede tumor relapse.

Oncolytic viruses (OVs) are increasingly recognized as potent tools in cancer therapy, effectively targeting and eradicating oncogenic conditions while sparing healthy cells. They enhance antitumor immunity by triggering various immune responses throughout the cancer cycle. Genetically engineered OVs swiftly destroy cancerous tissues and activate the immune system by releasing soluble antigens like danger signals and interferons. Their ability to stimulate both innate and adaptive immunity makes them particularly attractive in cancer immunotherapy. Recent advancements involve combining OVs with other immune therapies, yielding promising results. Transgenic OVs, designed to enhance immunostimulation and specifically target cancer cells, further improve immune responses. This review highlights the intrinsic mechanisms of OVs and underscores their synergistic potential with other immunotherapies. It also proposes strategies for optimizing armed OVs to bolster immunity against tumors.

Vesicles are loaded with a variety of cargoes, including membrane proteins, secreted proteins, signaling molecules, and various enzymes, etc. Not surprisingly, vesicle transport is essential for proper cellular life activities including growth, division, movement and cellular communication. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate membrane fusion of vesicles with their target compartments that is fundamental for cargo delivery. Recent studies have shown that multiple SNARE family members are aberrantly expressed in human cancers and actively contribute to malignant proliferation, invasion, metastasis, immune evasion and treatment resistance. Here, the localization and function of SNARE proteins in eukaryotic cells are firstly mapped. Then we summarize the expression and regulation of SNAREs in cancer, and describe their contribution to cancer progression and mechanisms, and finally we propose engineering botulinum toxin as a strategy to target SNAREs for cancer treatment.