HNSCC is the sixth most common cancer worldwide and the prognosis is still poor. Here, we investigated the prognostic implications of CDK7 and pMED1. Both proteins affect transcription, and their expression is altered throughout different tumor entities. pMED1 is phosphorylated by CDK7. Importantly, CDK7 and MED1 have been ascribed prognostic implications by various studies. However, their prognostic value in head and neck squamous-cell cancer (HNSCC) remains elusive. We applied immunohistochemical staining of CDK7 and pMED1 on our large and clinically well-characterized HNSCC tissue cohort comprising 419 patients. Software-aided quantification of staining intensity was performed as a measure of protein expression. The following results were linked to the clinicopathological features of our cohort and correlated in different tissue types (primary tumor, lymph node metastasis, distant metastasis, recurrence). Upregulation CDK7 was associated with worse 5-year overall survival as well as disease-free survival in HNSCC while being independent of other known prognostic factors such as p16-status. Also, CDK7 expression was significantly elevated in immune cell infiltrated tumors. In HNSCC CDK7 might serve as a novel prognostic marker to indicate the prognosis of patients. Furthermore, in vitro studies proved the feasibility of CDK7 inhibition with attenuating effects on cell proliferation underlining its remarkable translational potential for future therapeutic regimes.
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http://dx.doi.org/10.3390/cancers14030492 | DOI Listing |
CDK7 regulates RNA polymerase II (RNAPII) initiation, elongation, and termination through incompletely understood mechanisms. Because contaminating kinases precluded CDK7 analysis with nuclear extracts, we completed biochemical assays with purified factors. Reconstitution of RNAPII transcription initiation showed CDK7 inhibition slowed and/or paused RNAPII promoter-proximal transcription, which reduced re-initiation.
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February 2025
Department of Molecular and Cell Biology, University of California, Merced, Merced, CA, USA.
Tubulin polyglutamylation is essential for maintaining cilium stability and function, and defective tubulin polyglutamylation is associated with ciliopathies. However, the regulatory mechanism underlying proper axonemal polyglutamylation remains unclear. He et al.
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January 2025
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 406040, Taiwan; Institute of Biochemistry and Molecular Biology, China Medical University, Taichung, 406040, Taiwan. Electronic address:
Although breast cancer treatment has evolved significantly in recent years, drug resistance remains a major challenge. To identify new targets for breast cancer, we found that stage-specific embryonic antigen 4 (SSEA-4) is expressed in all subtypes of breast cancer cell lines, and the increased expression of the associated enzymes β3GalT5 and ST3Gal2 correlates with poor recurrence-free survival (RFS) in breast cancer. We also found that SSEA-4 antibodies can be rapidly internalized into breast cancer cells, a property that makes SSEA-4 an attractive target for antibody-drug conjugates (ADCs).
View Article and Find Full Text PDFBioorg Chem
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Department of Natural Products & Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, Telangana, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
Cyclin-dependent kinases, CDK7 and CDK9 play critical roles in cancer by regulating transcriptional processes essential for cell proliferation and survival. Their dysregulation leads to aberrant gene expression, promoting oncogenic pathways and contributing to tumor growth and progression. This study aimed to identify a new chemotype for CDK7/9 inhibitors using a structure-based virtual screening approach.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Otolaryngology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138, Sheng Li Road, Tainan, Taiwan, 70456.
Results of retinoid-based therapies in head and neck cancer (HNC) are generally disappointing, indicating a lack of understanding of retinoic acid signaling. The role of retinoic acid receptor gamma (RARγ) and its isoforms in HNC is yet to be established. In this study, we found that RARγ1, 2, 4 are the predominant RARγ isoforms expressed in various types of human cancers, including HNC.
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