Transcriptomics

Dataset Information

0

Expression data from parental MDA-MB-231 cells and MDA-MB-231(SA) variant


ABSTRACT: Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE20085 | GEO | 2010/04/19

SECONDARY ACCESSION(S): PRJNA124283

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2010-04-19 | E-GEOD-20085 | biostudies-arrayexpress
2021-11-04 | GSE144506 | GEO
2021-01-04 | PXD023142 | Pride
2023-07-20 | PXD017809 | Pride
2024-04-23 | GSE173270 | GEO
2019-03-01 | GSE111504 | GEO
2022-07-11 | GSE207435 | GEO
2008-06-17 | E-GEOD-8555 | biostudies-arrayexpress
2019-09-24 | GSE137842 | GEO
2024-07-05 | GSE263696 | GEO