The association between breast cancer risk and genetic variants of fibroblast growth factor receptor 2 (FGFR2) has been identified and repeatedly confirmed; however, the mechanism underlying FGFR2 in breast tumorigenesis remains obscure. Given that breast tumorigenesis is particularly related to DNA double-strand-break-repair (DSBR), we examined the hypothesis that FGFR2 is involved in DSBR. Our results show that expression of Mre11, a vital exonuclease in DSBR, is downregulated by FGFR2, which is further linked to decreased DSBR. Analysis of the Mre11 promoter revealed that POU1F1 mediates FGFR2-induced Mre11 downregulation. Furthermore, ERK, downstream of FGFR2, directly interacts with and phosphorylates POU1F1, increasing POU1F1 binding capacity to the Mre11 promoter and repressing Mre11 expression, which consequently affects DSBR and sensitizes breast cancer cells to chemotherapeutic treatments. The importance of the FGFR2-Mre11-DSBR link in cancer progression is suggested by the finding that genotypes of FGFR2 and Mre11 are associated with survival of breast cancer patients and that FGFR2 expression correlates with cancer prognosis specifically in patients receiving chemotherapy. This study yields important insight into the role of FGFR2 in breast tumorigenesis and may facilitate development of a useful therapeutic approach for breast cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/hmg/ddv102 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Investigating POU3F4 in cancer: Expression patterns, prognostic implications, and functional roles in tumor immunity.
Heliyon
January 2025
Department of Cardiothoracic Surgery, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng, 224002, China.
Research has demonstrated that POU3F4 is integral to various cancers, in addition to its significance in inner ear development, pancreatic differentiation, as well as neural stem cell differentiation. Nevertheless, comprehensive pan-cancer analyses focusing on POU3F4 remain limited. This study aims to assess the prognostic value of POU3F4 in thirty-three cancers and explore its immune-related functions.
View Article and Find Full Text PDFFOXR2 in cancer development: emerging player and therapeutic opportunities.
Oncol Res
January 2025
College of Food Sciences, Al-Qasim Green University, Babylon, Iraq.
Cancer, a leading cause of global mortality, remains a significant challenge to increasing life expectancy worldwide. Forkhead Box R2 (FOXR2), identified as an oncogene within the FOX gene family, plays a crucial role in developing various endoderm-derived organs. Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.
View Article and Find Full Text PDFActivation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers.
Biochemistry (Mosc)
December 2024
Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia.
Activation of the p38 mitogen-activated protein kinase (MAPK) pathways is vital in regulating cell growth, differentiation, apoptosis, and stress response, significantly affecting tumorigenesis and cancer progression. We developed a bioinformatic technique to construct an interactome network-based molecular pathways for genes of interest and quantify their activation levels using high-throughput gene expression data. This study is focused on the p38α, p38β, p38γ, and p38δ kinases, examining their activation levels (PALs) based on transcriptomic data and their associations with survival and drug responsiveness across various cancer types.
View Article and Find Full Text PDFUrchin-like magnetic nanoparticles loaded with type X collagen siRNA and Stattic to treat triple negative breast cancer under rotating magnetic field like an "enchanted micro-scalpel".
Int J Biol Macromol
January 2025
Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710100, Shaanxi, PR China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518063, PR China. Electronic address:
Magnetic nanoparticles effectively target drug delivery, contrast agents, biosensors, and more. Urchin-like magnetic nanoparticles (UMN) with abundant spike-like structures exhibit superior magneto-mechanical force to destroy tumor cells compared with other shapes of magnetic nanoparticles. However, when cell contents are released from tumor cells induced by magneto-mechanical force, they can act on surrounding tumor cells to facilitate tumor development.
View Article and Find Full Text PDFDandelion extract suppresses the stem-like properties of triple-negative breast cancer cells by regulating CUEDC2/β-catenin/OCT4 signaling axis.
J Ethnopharmacol
January 2025
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Department of Integration of Chinese and Western Medicine, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address:
Ethnopharmacological Relevance: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, featuring a high proportion of cancer stem cells (CSCs) and the poorest clinical outcomes. Taraxacum mongolicum Hand. -Mazz.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!