bims-metorg 2026-02-22 papers

Issue of 2026–02–22
four papers selected by
Bruna Martins Garcia, CABIMER

Nat Rev Cancer. 2026 Feb 20.

Decoding cancer across scales with metabolomics.

It is well established that malignant cells alter their metabolism to support proliferation, but the nutrients required to meet the anabolic demands of different cancers located at various anatomical sites throughout the body remain largely unknown. Moreover, the extent to which nutrients are supplied by neighbouring stromal cells or distant tissues, possibly due to metabolic reprogramming, is poorly understood. Metabolomics provides a unique biochemical approach to address these gaps in our knowledge, but cancer studies require careful consideration because it is challenging to identify appropriately matched control samples for comparison. Here, we detail a collection of metabolomics workflows designed to interrogate cancer across three discrete scales. First, we describe experiments to define the nutrient demands of cancer cells themselves. Second, we focus on identifying metabolic relationships between neighbouring cells in the tumour microenvironment. Finally, we highlight strategies to explore the metabolic crosstalk between cancer cells and distant tissues in the tumour macroenvironment. The approaches outlined span cells in culture, animal models and human specimens from patients with cancer. Special emphasis is dedicated to the application of emerging technologies and computational pipelines in the field of mass spectrometry that enable global profiling of metabolites and lipids.

DOI: https://doi.org/10.1038/s41568-026-00908-0

Clin Chim Acta. 2026 Feb 15. pii: S0009-8981(26)00076-8. [Epub ahead of print]586 120894

Circulating integrins as biomarkers for bone metastasis in prostate cancer.

Bandar Theyab Alenezi, Abdullah R Alzahrani, Zia Ur Rehman, Shatha Alzahrani, Hayaa M Alhuthali, Amani A Alrehaili, Abdul Hai, Mohd Imran.

Bone complications are characteristic clinical complications of prostate cancer and a significant predictor of disease progression, morbidity, and patient care. Despite advancements in imaging and systemic therapies, current laboratory-based diagnostic methods, which predominantly focus on prostate-specific antigen (PSA), conventional radiology, and bone turnover markers, remain inadequate for the early correction of laboratory-based risk, identification of micrometastatic disease, and continuous monitoring of biochemical evidence of skeletal involvement in patients with metastatic castration-resistant prostate cancer (mCRPC). This diagnostic gap has heightened interest in circulating biomarkers that are analytically accessible and capable of recapitulating the biological mechanisms underlying bone-tropic metastatic progression. Mechanistic and clinical investigations have demonstrated that specific integrin subtypes generate a molecular signature associated with skeletal colonization by metastatic cells. This signature encompasses processes such as vascular arrest, transendothelial migration, adhesion to bone matrix components, and interactions with osteoblastic, immune, and stromal niches, all of which are reproducible and quantifiable. Integrins also appear in clinically relevant biofluids and cellular compartments, such as circulating tumor cells, extracellular vesicles, and bone marrow-resident disseminated tumor cells. This review synthesizes human clinical, translational, and population-based data linking circulating integrin-related signals with metastatic risk, disease progression, and outcomes associated with tumors and the skeletal system in patients with prostate cancer. We conducted a critical review of laboratory findings derived from liquid biopsies, including integrin-positive circulating tumor cells, extracellular vesicle-bound integrins, circulating extracellular matrix components, and integrin-regulated transcriptional and microRNA signatures. These findings were rigorously analyzed in terms of their diagnostic and prognostic efficacy compared to established clinical biomarkers. Registry-based and real-world evidence also highlights the clinical and laboratory implications of a failure to detect skeletal degeneration in a timely manner, which facilitates the consideration of integrin-related circulating markers as an add-on to diagnostic laboratory medicine processes.

Keywords: Bone metastasis; Circulating biomarkers; Circulating tumor cells; Extracellular vesicles; Integrin receptors; Liquid biopsy; Prostate cancer

DOI: https://doi.org/10.1016/j.cca.2026.120894

Biochem Biophys Res Commun. 2026 Feb 14. pii: S0006-291X(26)00192-0. [Epub ahead of print]808 153428

Mapping metastatic potential through cytoskeletal remodeling: A mechanobiology-based multi-cancer analysis.

Ksenia Maksimova, Margarita Pustovalova, Denis V Kuzmin, Sergey Leonov, Yulia Merkher.

Metastasis remains the leading cause of cancer-related mortality, yet current clinical tools lack sensitivity for early detection of metastatic potential. While gene expression assays have improved prognostic stratification in select cancers, they often overlook dynamic cellular behaviors such as cytoskeletal remodeling and mechanotransduction. We curated a panel of 11 mechanobiology-related genes involved in actin cytoskeleton regulation and evaluated their predictive value using multi-modal data from the DepMap database, including gene expression, copy number variation, CRISPR, and RNAi screens. Analyses were conducted across 351 cell lines from breast, pancreatic, and central nervous system (CNS) tumors, stratified by tumor type and MetMap-derived metastatic potential. Gene expression and CNV emerged as the most informative parameters for distinguishing metastatic potential. Among the candidate genes, FSCN1 consistently demonstrated strong associations across tissues, classification schemes, and correlation with canonical metastasis markers. MYH9, ECM1, ANXA2, and EZR also showed robust performance, particularly in cumulative multi-gene signatures. Correlation analyses revealed significant positive correlations with invasion, EMT, stemness markers (e.g., MMP2, VIM, CD44), and inverse correlations with epithelial markers (e.g., CDH1, EPCAM), reinforcing the biological coherence of the panel. Our study introduces a previously unrecognized, mechanobiologically driven gene panel - FSCN1, MYH9, ECM1, ANXA2, and EZR - as a cross-cutting biomarker signature of metastatic potential, applicable across multiple cancer types. Unlike conventional markers that often reflect tumor-specific traits, this panel captures the mechanical and structural determinants of cell invasiveness. The robustness of these genes across diverse molecular assays and their alignment with core metastatic pathways underscore their translational relevance.

Keywords: Actin cytoskeleton remodeling; DepMap; Mechanobiology; MetMap; Metastatic potential; Prognostic biomarkers

DOI: https://doi.org/10.1016/j.bbrc.2026.153428

Biosci Rep. 2026 Feb 18. pii: BSR20253516. [Epub ahead of print]46(2):

The role of growth hormone in metastasis and angiogenesis of breast cancer.

Tamanna Alam, Mingyang Hu, Rivka L Isaacson.

Breast cancer is a complex disease which has many factors affecting its progression and metastasis. Although steroid hormones, especially oestrogen, are most commonly associated with breast cancer, growth hormone (GH) also plays a substantial role in its development and spread via the activation of downstream signalling pathways and the regulation of growth factors such as insulin-like growth factor-1 (IGF-1) and the vascular endothelial growth factor (VEGF). Breast cancer patients usually have elevated levels of GH and IGF-1 in their circulation. Growth hormone receptor (GHR) signalling enhances migratory ability of tumour cells and excess IGF-1 production promotes angiogenesis. Gaining a full understanding of the mechanisms behind GH and breast cancer will allow researchers to develop more therapeutics to treat this devastating disease.

Keywords: angiogenesis; breast cancers; growth hormones; insulin-like growth factor; metastasis

DOI: https://doi.org/10.1042/BSR20253516