bims-metorg 2025-11-16 papers

Issue of 2025–11–16
two papers selected by
Bruna Martins Garcia, CABIMER

Elife. 2025 Nov 12. pii: RP103697. [Epub ahead of print]13

Rearrangement of 3D genome organization in breast cancer epithelial to mesenchymal transition and metastasis organotropism.

Priyojit Das, Rebeca San Martin, Tian Hong, Rachel Patton McCord.

Human breast cancer cells exhibit organotropism during metastasis, showing preferential homing to certain organs such as bone, lung, liver, and brain. Spatial genome organization plays a crucial role in oncogenic transformation and progression, but the extent to which chromosome architecture contributes to organ-specific metastatic traits is unclear. This work characterizes chromosome architecture changes associated with organotropic metastatic traits. By comparing a collection of human genomic data from different subtypes of localized and lung metastatic breast cancer cells with both normal and cancerous lung cells, we find important trends of genomic reorganization. The most striking differences in 3D genome compartments segregate cell types according to their epithelial vs. mesenchymal status. This epithelial-mesenchymal transition (EMT) compartment signature occurs at genomic regions distinct from transcription-defined EMT signatures, suggesting a separate layer of regulation. Specifically querying organotropism, we find 3D genome changes consistent with adaptations needed to survive in a new microenvironment, with lung metastatic breast cancer cells exhibiting compartment switch signatures that shift the genome architecture to a lung cell-like conformation and brain metastatic prostate cancer cells showing compartment shifts toward a brain-like state. TCGA patient data reveals gene expression changes concordant with these organ-permissive compartment changes. These results suggest that genome architecture provides an additional level of cell fate specification informing organotropism and enabling survival at the metastatic site.

Keywords: 3D genome; EMT; breast cancer; cancer biology; chromosome compartmentalization; chromosomes; gene expression; human; metastasis; organotropism

DOI: https://doi.org/10.7554/eLife.103697

Cell Mol Immunol. 2025 Nov 10.

IL33-induced lipid droplet formation in mature low-density neutrophils drives colorectal cancer liver metastasis.

Yuchen Zhang, Suyue Yu, Dina Yeernuer, Wangyi Liu, Zhuoqing Xu, Wenqing Feng, Zeping Lv, Xuanhao Liu, Peiqi Tan, Minhua Zheng, Yaping Zong, Aiguo Lu, Jingkun Zhao.

The microenvironment of distant organs affects the colonization and growth of disseminated tumor cells. It remains unclear how tumor-associated neutrophils are influenced by the microenvironment of distant organs. Here, we demonstrate that mature low-density neutrophils in colorectal cancer patients abnormally accumulate neutral lipids and induce the reactivation of dormant tumor cells, a process regulated by hepatic stellate cells. Mechanistically, activated hepatic stellate cells increased DGAT1/2-dependent lipid droplet synthesis in low-density neutrophils through the secretion of IL33, thereby maintaining the survival and immunosuppressive function of these neutrophils. The uptake of lipids from lipid-laden low-density neutrophils drives dormant tumor cell reactivation through the potentiation of β-oxidation and the stimulation of protumorigenic eicosanoid synthesis. In mouse models, targeting IL33 blocked neutrophil lipid synthesis, decreased the colonization of colorectal cancer cells in the liver, and enhanced the efficacy of immunotherapy. Overall, our study revealed that lipid accumulation in mature low-density neutrophils regulates the growth of dormant tumor cells and antitumor immunity to facilitate colorectal cancer liver metastasis. Targeting IL33 could be a promising therapeutic approach for colorectal cancer liver metastases.

Keywords: colorectal cancer; lipid droplets; liver metastasis; mature low-density neutrophils; metabolic reprogramming

DOI: https://doi.org/10.1038/s41423-025-01365-9