Publication

Ki-67 promotes circulating tumor cell intravasation and metastasis in breast cancer

2026

Abstract

Ki-67, a canonical proliferation marker, represents a pivotal prognostic and predictive biomarker in breast cancer. Here, by profiling 88,208 single-cell transcriptomes of circulating tumor cells (CTCs) matched with primary and metastatic lesions in breast cancer mouse models, we uncover a striking enrichment of cell-cycle genes in CTCs, particularly in CTC clusters. Using in vivo CRISPR screens, we identify Ki-67 as an essential regulator of CTC intravasation, whose knockout reduces metastasis. Mechanistically, Ki-67 depletion does not curb proliferation but suppresses genes involved in maintaining cell-cell adhesion, including CD47 and KLF4, thereby linking its expression to collective invasion dynamics. Altogether, decoupling it from its role as a proliferation marker, our findings uncover an unexpected function of Ki-67 as a molecular driver of metastatic competence.

Official source

https://infoscience.epfl.ch/entities/publication/efd1f86e-e4d1-4f9f-af4a-bb18d3f05ecd

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2026

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/efd1f86e-e4d1-4f9f-af4a-bb18d3f05ecd

About this result

Related concepts (32)

Metastatic breast cancer

Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; there is no stage after IV. Metastases can occur several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed.

Metastasis

Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues. Cancer occurs after cells are genetically altered to proliferate rapidly and indefinitely.

Mouse models of breast cancer metastasis

Breast cancer metastatic mouse models are experimental approaches in which mice are genetically manipulated to develop a mammary tumor leading to distant focal lesions of mammary epithelium created by metastasis. Mammary cancers in mice can be caused by genetic mutations that have been identified in human cancer. This means models can be generated based upon molecular lesions consistent with the human disease. Metastasis is a process of migration of tumour cells from the primary cancer site to a distant location where the cancer cells form secondary tumors.