bims-merabr 2026-06-21 papers

Cancer Biol Ther. 2026 Dec 31. 27(1): 2688544

STARD10 promotes progression of HER2+ breast cancer and intracellular lipid metabolism via the cAMP/PKA/CREB1 signaling axis.

Siyao Liu, Jing Gao, Yichen Niu, Xinnan Dong, Zhiming Zhang, Xiao Teng, Zhaorong Li, Siyan Zhang, Yong Meng, Ming-Qing Gao.

BACKGROUND: Although targeted therapies have improved clinical outcomes, HER2+ breast cancer remains a significant clinical challenge due to its aggressive behavior and unfavorable prognosis. Emerging evidence indicates that dysregulated lipid metabolism plays a critical role in tumorigenesis and metastasis, suggesting that targeting lipid metabolism may represent a promising therapeutic strategy. STARD10, a lipid transport protein, plays a pivotal role in regulating lipid metabolism. However, its function in mediating lipid metabolism and tumor progression in HER2+ breast cancer remains unclear.
METHODS: The expression level and prognostic relevance of STARD10 in HER2+ breast cancer were analyzed using public databases and clinical cohorts. CCK-8, EdU, colony formation, transwell, LD540, and Nile Red staining assays were performed in SKBR3 and HCC1954 cells. Subcutaneous implantation and tail vein injection were performed to evaluate the effects of STARD10 overexpression on tumor growth and lung metastasis in vivo. The mechanism was validated by RNA-seq and Western blotting.
RESULTS: STARD10 expression was upregulated in HER2+ breast cancer tissues and was significantly correlated with poor prognosis. Functionally, STARD10 overexpression enhanced HER2+ breast cancer cell proliferation, migration, invasion, and lipid droplets accumulation. Moreover, STARD10 overexpression markedly accelerated tumor growth and lung metastasis in vivo. Mechanistically, STARD10 was found to drive malignant phenotypes via activation of the cAMP/PKA/CREB1 signaling axis.
CONCLUSION: STARD10 promotes malignant progression of HER2+ breast cancer and lipid droplets accumulation by activating the cAMP/PKA/CREB1 pathway. These findings suggest that STARD10 and the cAMP/PKA/CREB1 signaling axis as potential therapeutic targets for the treatment and prevention of HER2+ breast cancer.

Keywords: HER2+ breast cancer; STARD10; cAMP/PKA/CREB1; lipid droplets; tumor progression

DOI: https://doi.org/10.1080/15384047.2026.2688544

Transl Cancer Res. 2026 May 30. 15(5): 392

COL10A1 overexpression potentially contributes to poor outcomes in breast cancer via autophagy and vasculogenic mimicry.

Liu Gao, Jingrui Yang, Xinru Fan, Yu Ling, Xu Jiang, Xin Jin, Hui Xu, Yunzhi Ling, Li Yu.

Background: Although the in-depth study of breast cancer pathogenesis has led to progress in therapies and improved outcomes in recent decades, new treatment methods are needed, especially for incurable metastatic breast cancer. Studies have proven that collagen X alpha 1 chain (COL10A1) expression is elevated in various malignant tumors, but COL10A1 has not been systematically analyzed in breast cancer. We investigated the effects of COL10A1 on breast cancer development and the mechanisms involved.
Methods: We analyzed COL10A1 expression through the cancer database, and collected serum and tumour tissue specimens from patients with breast cancer to evaluate COL10A1's expression and correlation with clinicopathology. COL10A1 expression in breast cancer cell lines was assessed at the cellular level, and stable transient cell lines were constructed for autophagy examination in breast cancer cells using immunofluorescence and Western blotting. Tubulation assay and Western blotting were used to detect changes in vasculogenic mimicry (VM). Different experiments evaluated COL10A1's effects on breast cancer cell proliferation, migration, and invasiveness. A subcutaneous transplantation nude mouse tumor model was constructed, and changes in tumor volume and mass were recorded, while changes in the expression of vascular growth mimetic genes were examined using Western blotting.
Results: Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases revealed COL10A1 upregulation in different breast cancer subtypes. Kaplan-Meier Plotter analysis showed that patients with elevated COL10A1 expression had poorer survival. Clinical tests found that COL10A1 expression in tumor specimens from patients with breast cancer was significantly higher than in controls and was closely associated with clinicopathology features, such as histological grading, tumor-node-metastasis (TNM) stage, and distant lymph node metastasis. Western blot analysis and other experiments revealed that low COL10A1 expression inhibited autophagy and VM in breast cancer cells, which inhibited breast cancer proliferation, apoptosis, migration, and invasion. High COL10A1 expression had opposite effects. Animal experiments showed that tumors from the high COL10A1 expression group were significantly larger than those from the control group.
Conclusions: COL10A1 may be involved in breast cancer cell proliferation, apoptosis, invasion and migration, which are related to autophagy and VM, suggesting that COL10A1 may serve as a novel target for clinical breast cancer therapy.

Keywords: Breast cancer; Collagen X alpha 1 chain (COL10A1); angiogenic mimicry; autophagy

DOI: https://doi.org/10.21037/tcr-2025-aw-2165

Mol Biol Rep. 2026 Jun 18. pii: 943. [Epub ahead of print]53(1):

The role of fibroblast growth factor 21 in diabetes and metabolic dysfunction.

Ashirvad Jaiswal, Chadani Nigam, Gaurish Narayan Singh, Anurag Kumar Gautam.

Fibroblast growth factor 21 (FGF21) is an endocrine hormone central to metabolic regulation under nutritional and cellular stress. Predominantly synthesized by the liver, FGF21 exerts pleiotropic effects through fibroblast growth factor receptor 1c (FGFR1c) and its co receptor β-Klotho, targeting adipose tissue, skeletal muscle, pancreas, and the central nervous system. In diabetes mellitus, FGF21 enhances insulin sensitivity, stimulates adiponectin secretion, alleviates hepatic steatosis, and protects pancreatic β-cells from oxidative and endoplasmic reticulum stress. These effects are mediated via key molecular pathways, including AMPK, SIRT1, PGC-1α, and mTOR signaling. Interestingly, despite elevated circulating FGF21 levels in obesity and type 2 diabetes, biological responsiveness is diminished-a phenomenon termed FGF21 resistance, characterised by impaired receptor expression, inflammatory signaling interference, and downstream signaling deficits. This review presents an in depth mechanistic overview of FGF21 signaling, its regulatory networks, and implications for glucose and lipid homeostasis, inflammation, mitochondrial health, and autophagy. Additionally, it discusses the development of pharmacologically optimized FGF21 analogs and multi agonists designed to overcome resistance and enhance therapeutic efficacy. As our comprehension of FGF21 biology deepens, elucidation of its molecular processes, resistance phenomena, and pharmacological refinement will be crucial in establishing FGF21 as a fundamental element of precision medicine for metabolic illnesses. The incorporation of FGF21 based strategies with combinatorial pharmacotherapy and tissue targeted delivery methods offers a potential approach to tackle the complicated pathophysiology of diabetes and improve clinical outcomes in affected populations.

Keywords: Diabetes; Fibroblast growth factor 21; Inflammation; Metabolic diseases

DOI: https://doi.org/10.1007/s11033-026-12132-y

Curr Cancer Drug Targets. 2026 Jun 12.

NRF2-Driven CARM1 Promotes Malignant Progression and Ferroptosis Resistance in Breast Cancer.

Yin Zhang, Yinan Guan, Hao Yu, Tingting Zhu, Shengjia Wang, Xiaohan Cheng, Jingjing Ma.

BACKGROUND: CARM1 has attracted significant attention due to its role in carcinogenesis across a variety of cancers. Ferroptosis has emerged as a prospective target in anticancer therapy.
OBJECTIVE: This study aimed to investigate the role of CARM1 in TNBC progression and ferroptosis regulation, as well as to clarify the underlying molecular mechanism involving NRF2-mediated transcriptional activation of CARM1.
METHODS: This study combined bioinformatics analysis, in vitro experiments, and in vivo validation to investigate the role of the NRF2-CARM1 axis in TNBC. Public datasets (UCSC Xena, GEPIA2) were analyzed for CARM1/NRF2 expression, correlation, and prognosis. CARM1 and NRF2 were manipulated in BC cells using siRNA/shRNA and overexpression plasmids. Proliferation, migration, and invasion were assessed by CCK-8, colony formation, wound healing, and Transwell assays. Cell apoptosis was assessed via flow cytometry and immunoblotting analysis. Ferroptosis was quantified by lipid peroxidation (TBARS), lipid ROS (BODIPY 581/591 C11), and total iron levels, together with immunoblotting of ferroptosis-related molecules. NRF2 binding to the CARM1 promoter was examined by ChIP and luciferase reporter assays using wild-type (WT) and NRF2-binding-site mutant (MUT) promoter constructs. A xenograft model was used to validate in vivo relevance.
RESULTS: CARM1 and NRF2 were elevated in BC tissues and cells. CARM1 silencing inhibited proliferation, migration, and invasion in BC cells while facilitating cell apoptosis and ferroptosis, as evidenced by increased lipid peroxidation, lipid ROS accumulation, and iron levels. NRF2 positively regulated CARM1 expression and enhanced WT CARM1 promoter activity, whereas mutation of the NRF2-binding site abolished this effect. ChIP further confirmed enrichment of the CARM1 promoter region in NRF2 immunoprecipitates, supporting direct transcriptional activation of CARM1 by NRF2. Functionally, NRF2 overexpression partially rescued the anti-tumor and pro-ferroptotic effects caused by CARM1 depletion. In vivo, CARM1 knockdown inhibited tumor growth and enhanced lipid peroxidation, which was partially reversed by NRF2 overexpression.
DISCUSSION: These findings identify a novel NRF2-CARM1 regulatory axis involved in TNBC progression and ferroptosis resistance. NRF2 directly activates CARM1 transcription, thereby promoting malignant behaviors and suppressing ferroptotic cell death in TNBC cells. These results improve the understanding of TNBC biology and suggest that the NRF2- CARM1 pathway may serve as a potential therapeutic target for ferroptosis-based treatment strategies.
CONCLUSION: NRF2 directly binds to and transcriptionally activates CARM1, thereby enhancing ferroptosis resistance and promoting TNBC progression. These findings reveal a novel molecular mechanism underlying TNBC malignancy and suggest that targeting the NRF2-CARM1 axis, particularly in combination with ferroptosis inducers, may provide a potential strategy for TNBC treatment.

Keywords: CARM1; NRF2; TNBC; ferroptosis; invasion.; migration

DOI: https://doi.org/10.2174/0115680096452329260608045835