Senescent cells promote breast cancer cells motility by secreting GM-CSF and bFGF that activate the JNK signaling pathway Journal Article
| Authors: | Wang, N.; Fang, Y.; Hou, Y.; Cheng, D.; Dressler, E. V.; Wang, H.; Wang, J.; Wang, G.; Li, Y.; Liu, H.; Xiang, R.; Yang, S.; Sun, P. |
| Article Title: | Senescent cells promote breast cancer cells motility by secreting GM-CSF and bFGF that activate the JNK signaling pathway |
| Abstract: | Background: Cellular senescence can be induced in mammalian tissues by multiple stimuli, including aging, oncogene activation and loss of tumor suppressor genes, and various types of stresses. While senescence is a tumor suppressing mechanism when induced within premalignant or malignant tumor cells, senescent cells can promote cancer development through increased secretion of growth factors, cytokines, chemokines, extracellular matrix, and degradative enzymes, collectively known as senescence-associated secretory phenotype (SASP). Previous studies indicated that senescent cells, through SASP factors, stimulate tumor cell invasion that is a critical step in cancer cell metastasis. Methods: In the current study, we investigated the effect of senescent cells on the motility of breast cancer cells, which is another key step in cancer cell metastasis. We analyzed the motility of breast cancer cells co-cultured with senescent cells in vitro and metastasis of the breast cancer cells co-injected with senescent cells in orthotopic xenograft models. We also delineated the signaling pathway mediating the effect of senescent cells on cancer cell motility. Results: Our results indicate that senescent cells stimulated the migration of breast cancer cells through secretion of GM-CSF and bFGF, which in turn induced activation of the JNK pathway in cancer cells. More importantly, senescent cells promoted breast cancer metastasis, with a minimum effect on the primary tumor growth, in orthotopic xenograft mouse models. Conclusions: These results have revealed an additional mechanism by which senescent cells promote tumor cell metastasis and tumor progression, and will potentially lead to identification of novel targets for cancer therapies that suppress metastasis, the major cause of cancer mortality. © The Author(s) 2024. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; human cell; genetics; nonhuman; mouse; animal; metabolism; animals; mice; metastasis; breast cancer; gene expression; map kinase signaling system; granulocyte macrophage colony stimulating factor; animal experiment; cell motion; pathology; cell line, tumor; breast neoplasms; enzyme linked immunosorbent assay; cancer mortality; extracellular matrix; fibroblast growth factor 2; xenograft; nude mouse; mice, nude; cerebrospinal fluid; breast tumor; cancer cell; tumor cell line; western blotting; cell migration; cell movement; senescence; tumor growth; cell aging; cell invasion; cell motility; migration; coculture; gm-csf; epithelial mesenchymal transition; granulocyte-macrophage colony-stimulating factor; rna isolation; cellular senescence; jnk; mapk signaling; senescence-associated secretory phenotype; humans; human; female; article; immunofluorescence assay; bfgf; mcf-7 cell line; basic fibroblast growth factor receptor; mda-mb-231 cell line; mda-mb-468 cell line; real time reverse transcription polymerase chain reaction; wound healing assay; jnk signaling |
| Journal Title: | Cell Communication and Signaling |
| Volume: | 22 |
| ISSN: | 1478-811X |
| Publisher: | BioMed Central Ltd. |
| Date Published: | 2024-10-07 |
| Start Page: | 478 |
| Language: | English |
| DOI: | 10.1186/s12964-024-01861-x |
| PUBMED: | 39375718 |
| PROVIDER: | scopus |
| PMCID: | PMC11457416 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
