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Publication : Follistatin-like 1 deficiency impairs T cell development to promote lung metastasis of triple negative breast cancer.

First Author  Ma J Year  2021
Journal  Aging (Albany NY) Volume  13
Issue  5 Pages  7211-7227
PubMed ID  33639614 Mgi Jnum  J:331218
Mgi Id  MGI:6751353 Doi  10.18632/aging.202579
Citation  Ma J, et al. (2021) Follistatin-like 1 deficiency impairs T cell development to promote lung metastasis of triple negative breast cancer. Aging (Albany NY) 13(5):7211-7227
abstractText  Our study aims to detect the underlying mechanism of the suppressive effect of Follistatin-like 1 (FSTL1) on lung metastasis of triple negative breast cancer (TNBC). We found that FSTL1 had no effect on the proliferation and metastasis of 4T1 cells in vitro, while in the tumor-bearing Fstl1 heterozygous (Fstl1(+/-)) mice, the number of anti-tumor T lymphocytes in the lung was significantly reduced with the increase in lung metastasis. Impaired development of T cells can cause dysfunction of adaptive immune system, which promotes cancer metastasis. Therefore the effect of FSTL1 on T cell development was further investigated. Lower population of T cells in periphery and decreased proliferation of CD4(-) CD8(-) double negative (DN) thymocytes and impairment development of T cells were found in Fstl1(+/-) mice. Furthermore, high expression of FSTL1 in medullary thymus epithelial (mTEC) cells and decreased mRNA expression of inducible costimulator on activated T-cell ligand (Icosl) in mTEC(sh Fstl1) were detected. Combining other studies that the generation of ICOSL by mTEC cells promotes CD4(+) single positive (SP) thymocytes to produce IL-2, which promotes T cell development. Our results indicate FSTL1 deficiency in mTEC cells impairs T cell development to promote the lung metastasis of TNBC.
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