Background: Nijmegen breakage syndrome (NBS) is a chromosomal-instability syndrome associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation. The NBS gene product, NBS1 (p95) or nibrin, is a part of the MRN complex, a central player associated with double-strand break (DSB) repair. We previously demonstrated that NBS1 overexpression contributes to transformation through the activation of PI 3-kinase/Akt. NBS1 overexpression also induces epithelial-mesenchymal transition through the Snail/MMP2 pathway.
Methods: RT-PCR, Western blot analysis, in vitro migration/invasion, soft agar colony formation, and gelatin zymography assays were performed.
Results: Here we show that heat shock protein family members, A4 and A14, were induced by NBS1 overexpression. siRNA mediated knockdown of HSPA4 or HSPA14 decreased the in vitro migration, invasion, and transformation activity in H1299 cells overexpressing NBS1. However, HSPA4 or HSPA14 induced activity was not mediated through MMP2. NBS1 overexpression induced the expression of heat shock transcription factor 4b (HSF4b), which correlated with the expression of HSPA4 and HSPA14.
Conclusion: These results identify a novel pathway (NBS1-HSF4b-HSPA4/HSPA14 axis) to induce migration, invasion, and transformation, suggesting the activation of multiple signaling events induced by NBS1 overexpression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022804 | PMC |
| http://dx.doi.org/10.1186/1423-0127-18-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Repeated ionizing radiation exposure induces TRIP13 expression, conferring radioresistance in lung cancer cells.
Sci Rep
January 2025
Reproductive Biology Laboratory, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands.
Radiation therapy is a common treatment modality for lung cancer, and resistance to radiation can significantly affect treatment outcomes. We recently described that lung cancer cells that express more germ cell cancer genes (GC genes, genes that are usually restricted to the germ line) can repair DNA double-strand breaks more rapidly, show higher rates of proliferation and are more resistant to ionizing radiation than cells that express fewer GC genes. The gene encoding TRIP13 appeared to play a large role in this malignant phenotype.
View Article and Find Full Text PDFeIF4E plays the role of a pathogenic gene in psoriasis, and the inhibition of eIF4E phosphorylation ameliorates psoriasis-like skin damage.
Exp Dermatol
January 2024
Department of Dermatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Psoriasis is a complex inflammatory skin disease with uncertain pathogenesis. eIF4E (eukaryotic translation initiation factor 4E) and its phosphorylation state p-eIF4E are highly expressed in psoriatic tissues. However, the role eIF4E played in psoriasis is still unclear.
View Article and Find Full Text PDFPhosphorylated Hsp27 promotes adriamycin resistance in breast cancer cells through regulating dual phosphorylation of c-Myc.
Cell Signal
December 2023
Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China. Electronic address:
Article Synopsis
- Chemotherapy resistance in breast cancer significantly impacts survival rates, with Heat shock protein 27 (Hsp27) implicated in this resistance, though its exact role is not fully understood.
- The study found that overexpression of Hsp27 in adriamycin-resistant breast cancer cells reduced DNA damage and cell death by promoting the stability and import of the c-Myc protein.
- Phosphorylation of Hsp27 during adriamycin treatment shifts it to the nucleus, where it enhances c-Myc levels and activates ATM, indicating Hsp27's crucial role in chemotherapy resistance in breast cancer.
Establishment and Characterization of Multi-Drug Resistant p53-Negative Osteosarcoma SaOS-2 Subline.
Diagnostics (Basel)
August 2023
Department of Pathology, Kazan State Medical University, Kazan 420012, Russia.
Aim: To establish a p53-negative osteosarcoma (OS) SaOS-2 cellular subline exhibiting resistance to specific chemotherapeutic agents, including topoisomerase II inhibitors, taxanes, and vinca alkaloids.
Methods: The OS subline exhibiting resistance to the chemotherapeutic agents indicated above was generated by the stepwise treatment of the parental SaOS-2 cell line with increasing concentrations of doxorubicin (Dox) for 5 months. Half-inhibitory concentrations (IC) for Dox, vinblastine (Vin), and paclitaxel (PTX) were calculated by a colorimetric MTS-based assay.
The Multiple Faces of the MRN Complex: Roles in Medulloblastoma and Beyond.
Cancers (Basel)
July 2023
Department of Molecular Medicine, University La Sapienza, 00161 Rome, Italy.
Hypomorphic mutations in MRN complex genes are frequently found in cancer, supporting their role as oncosuppressors. However, unlike canonical oncosuppressors, MRN proteins are often overexpressed in tumor tissues, where they actively work to counteract DSBs induced by both oncogene-dependent RS and radio-chemotherapy. Moreover, at the same time, genes are also essential genes, since the constitutive KO of each component leads to embryonic lethality.
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!