ArticleThe American journal of pathology2006
Signal transducers and activators of transcription-3 up-regulates tissue inhibitor of metalloproteinase-1 expression and decreases invasiveness of breast cancer.
Article in The American journal of pathology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- The Dual Roles of TIMP-1 in Cancer: From Protease Inhibition to Cytokine Signaling.Molecular biology reports · 2026Review
- Hepatic ceramide synthesis links systemic inflammation to organelle dysfunction in cancer.bioRxiv : the preprint server for biology · 2025Article
- Effects of Thyroid Hormones on Cellular Development in Human Ovarian Granulosa Tumor Cells (KGN).Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice.Nature metabolism · 2025Article
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
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- Targeting STAT-3 signaling pathway in cancer for development of novel drugs: Advancements and challenges.Genetics and molecular biology · 2020Article
- Transition into inflammatory cancer-associated adipocytes in breast cancer microenvironment requires microRNA regulatory mechanism.PloS one · 2017Article
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- Adenosine augments IL-10-induced STAT3 signaling in M2c macrophages.Journal of leukocyte biology · 2013Article
- An exposure to the oxidized DNA enhances both instability of genome and survival in cancer cells.PloS one · 2013Article
- Tissue microarray-based study of patients with lymph node-positive breast cancer shows tyrosine phosphorylation of signal transducer and activator of transcription 3 (tyrosine705-STAT3) is a marker of good prognosis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2012Article
- Leptin activates STAT3 and ERK1/2 pathways and induces endometrial cancer cell proliferation.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2011Article
- Upregulation of the signal transducers and activators of transcription 3 (STAT3) pathway in lymphatic metastases of papillary thyroid cancer.International journal of clinical and experimental pathology · 2011Article
- STAT3 knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7 expression in nude mice.PloS one · 2011Article
- STAT3 upregulates the protein expression and transcriptional activity of β-catenin in breast cancer.International journal of clinical and experimental pathology · 2010Article
- Matrix metalloproteinases and tissue inhibitor of metalloproteinases are essential for the inflammatory response in cancer cells.Journal of signal transduction · 2010Article
- Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship?.Annals of the New York Academy of Sciences · 2009Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal transducers and activators of transcription (STAT)-3 is an oncogenic protein that is constitutively activated in many human cancers, including 30 to 60% of primary breast cancer. The biological significance of STAT3 activation in breast cancer is not fully understood. We have previously shown that STAT3 up-regulates tissue inhibitors of metalloproteinase (TIMP)-1, a cytokine known to block metalloproteinases and decrease invasiveness in certain cancer cell types. We hypothesize that STAT3 activation may modulate tumor invasiveness of breast cancer by regulating TIMP1 expression. Using MCF-7 cells transfected with tetracycline-off STAT3C (constitutively active STAT3), we generated an in vitro system in which STAT3C levels can be tightly controlled in breast cancer cells. Increasing tetracycline levels gradually decreased STAT3C and TIMP1 in a dose-dependent manner, and down-regulation of these proteins led to a reciprocal decrease in invasiveness of these cells in Matrigel. Addition of a neutralizing anti-TIMP1 antibody increased invasiveness in the same experimental system. Using immunohistochemistry and 142 primary breast tumors, we found a significant association between the expression of the phosphorylated/active form of STAT3 (pSTAT3) and that of TIMP1. Importantly, STAT3 activation correlated significantly with a lower frequency of vascular and lymphatic invasion (P = 0.015 and P = 0.0002, respectively). Our data support the concept that STAT3 activation significantly modulates the biological and clinical behavior of breast cancer.
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