Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer cells frequently home to the bone marrow, where they may enter a dormant state before forming a bone metastasis. Several members of the interleukin-6 (IL-6) cytokine family are implicated in breast cancer bone colonization, but the role for the IL-6 cytokine leukaemia inhibitory factor (LIF) in this process is unknown. We tested the hypothesis that LIF provides a pro-dormancy signal to breast cancer cells in the bone. In breast cancer patients, LIF receptor (LIFR) levels are lower with bone metastases and are significantly and inversely correlated with patient outcome and hypoxia gene activity. Hypoxia also reduces the LIFR:STAT3:SOCS3 signalling pathway in breast cancer cells. Loss of the LIFR or STAT3 enables otherwise dormant breast cancer cells to downregulate dormancy-, quiescence- and cancer stem cell-associated genes, and to proliferate in and specifically colonize the bone, suggesting that LIFR:STAT3 signalling confers a dormancy phenotype in breast cancer cells disseminated to bone.
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PMID:Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow. 2778 4

Identification of pro-metastatic genomic alterations is urgently needed to help understand and prevent the fatal course of prostate cancer. Here, we found that the transcription factor EGR3, located at chromosome 8p21.3, is a critical metastasis suppressor. Aberrant deletion of EGR3 was found in up to 59.76% (deep deletions, 16.87%; shallow deletions, 42.89%) of prostate cancer patients. In informatics analysis, EGR3 loss was associated with prostate cancer progression and low survival rates. EGR3 expression inversely correlated with the expressions of epithelial-to-mesenchymal transition (EMT) and metastasis-related gene sets in prostate cancer tissues. In prostate cancer cells, EGR3 blocked the EMT process and suppressed cell migration and invasion. In a mouse model for cancer metastasis, EGR3 overexpression significantly suppressed bone metastases of PC3 and 22Rv1 prostate cancer cells. Mechanistically, EGR3 transcriptionally activated ZFP36, GADD45B, and SOCS3 genes by directly binding to their promoter regions. The EMT-inhibitory and tumor-suppressive roles of the EGR3 downstream genes were identified through in vitro and in silico analyses. Together, our results showed that EGR3 may be a biomarker to predict clinical outcomes and that it plays an important role in the metastatic progression of prostate cancer.
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PMID:Loss of EGR3 is an independent risk factor for metastatic progression in prostate cancer. 3279 59