Ask about this productRelated genes to: AMA1 protein
- Gene:
- SKA3 NIH gene
- Name:
- spindle and kinetochore associated complex subunit 3
- Previous symbol:
- C13orf3
- Synonyms:
- MGC4832, RAMA1
- Chromosome:
- 13q12.11
- Locus Type:
- gene with protein product
- Date approved:
- 2003-01-16
- Date modifiied:
- 2016-10-05
Related products to: AMA1 protein
Related articles to: AMA1 protein
- Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains associated with poor prognosis despite therapeutic advances. Protein palmitoylation, particularly reversible S-palmitoylation, modulates oncogenic signaling, membrane localization, and immune checkpoint stability, but the prognostic landscape of palmitoylation-related genes (PRGs) in LUAD and their relationship with the tumor microenvironment are not well defined. - Source: PubMed
Publication date: 2026/04/29
Wu ChaopengWang JinsongLiu YihanNi ZihanZhan YujieFeng WanyingFeng JiaPeng Min - Laryngeal squamous cell carcinoma (LSCC) is one of the most common types of head and neck cancer, posing a significant threat to public health. The spindle and kinetochore-associated complex subunit 3 (SKA3), a microtubule-binding subcomplex of the outer kinetochore, participates in cancer progression. However, its role in the progression of LSCC remains unclear. This study aimed to investigate the regulatory effects of SKA3 on LSCC progression and its underlying mechanism. In this study, the expression levels of SKA3 and aldo-keto reductase family 1 member C1 (AKR1C1) mRNA were assessed by quantitative real-time PCR. Protein expression was evaluated using western blotting. Cell proliferation was analyzed using the cell counting kit-8 assay, while apoptosis was assessed by flow cytometry. Cell migration and invasion were measured via Transwell assays. The levels of Fe2+ and glutathione were analyzed with colorimetric assays, while reactive oxygen species (ROS) levels were determined by flow cytometry. Chromatin immunoprecipitation and dual-luciferase reporter assays were employed to explore the interaction between SOX9 and SKA3. The impact of SKA3 silencing and AKR1C1 overexpression on tumor formation was investigated using a xenograft mouse model. The results showed that SKA3 expression was elevated in LSCC tissues and cells when compared with corresponding normal tissues and human nasopharyngeal epithelial cells. Silencing SKA3 suppressed LSCC cell proliferation, migration, and invasion, while promoting apoptosis and ferroptosis. SKA3 upregulated AKR1C1, a key ferroptosis-related gene, in TU177 and AMC-HN-8 cells. Overexpression of AKR1C1 mitigated the effects of SKA3 silencing on the malignant phenotypes of these cells. SOX9 was identified as a transcriptional activator of SKA3 in TU177 and AMC-HN-8 cells, and AKR1C1 overexpression reversed the inhibitory effect of SKA3 silencing on tumor growth in vivo. Thus, SKA3 played a pivotal role in the progression of LSCC through the SOX9/SKA3/AKR1C1 axis, suggesting that targeting SKA3 might have significant clinical implications for the treatment of LSCC. - Source: PubMed
Peng JingPan ZeyingRuan YanTang Chao - Familial prostate cancer (PCa) accounts for nearly 20% of all PCa cases and is associated with increased genetic susceptibility and earlier disease onset. However, early detection and risk stratification in genetically predisposed individuals remain challenging. Circulating cell-free DNA (cfDNA) provides a minimally invasive source of tumor-derived genomic and epigenomic information. Integrating multi-omic cfDNA analyses may enhance the discovery of biomarkers relevant to familial PCa biology. We conducted a pilot feasibility study employing whole-genome, strand-specific sequencing of cfDNA from eight patients with familial PCa. A unified analytical pipeline was used to jointly profile genomic alterations and epigenomic features. Variant calling, methylation mapping, and allele-specific methylation (ASM) analysis were performed to identify somatic mutations, characterize epigenetic dysregulation, and explore potential interactions between genetic and epigenetic mechanisms. Sequencing revealed 18,878 genetic variants, including 2276 potentially pathogenic alterations. We identified 26 recurrent high-impact mutations, such as stop-gain and start-loss variants, in genes including , , and . Epigenomic profiling demonstrated widespread gene-specific hypermethylation, consistent with transcriptional repression in these loci. ASM events were detected in , , , , and , suggesting coordinated interactions between somatic variation and epigenetic regulation in familial PCa. This proof-of-concept study highlights the feasibility and potential of integrating whole-genome and epigenome profiling of cfDNA to decode the molecular architecture of familial prostate cancer. By jointly capturing genomic alterations and epigenetic signatures, including allele-specific methylation, this multi-omic liquid biopsy approach supports a high-resolution exploration of biologically relevant molecular features. Moreover, this integrated profiling strategy provides a minimally invasive and clinically scalable tool that may substantially improve risk assessment. These findings offer a promising foundation for future validation studies in larger cohorts, with the aim of advancing multi-omic cfDNA analysis as a next-generation technology in the field of precision oncologic epigenetics. - Source: PubMed
Publication date: 2026/04/03
Truda AnnaCordella AngelaDe Leo IleniaDi Palo ArmandoIorio RobertaMarino SimonaLa Rocca RobertoCollà Ruvolo ClaudiaPotenza NicolettaRavo MariaMarchese Giovanna - CRISPR screens are a powerful functional genomics approach for identifying genes that confer sensitivity and resistance to anti-cancer therapies. CFI-402257 (luvixasertib, 2257) is a small molecule inhibitor of threonine tyrosine kinase (TTK), a promising therapeutic target in genomically unstable cancers due to its critical role in establishing the spindle assembly checkpoint (SAC) during mitosis. To inform its ongoing development and evaluation in clinical trials, we sought to use CRISPR activation (i.e., gain of function) screens to identify cellular mechanisms of resistance to 2257 in models of triple-negative breast cancer (TNBC). In vitro screens conducted in two TNBC cell lines nominated ABCG2 as the top resistance-conferring gene in both models. Validation studies assessing clonogenic survival and apoptosis confirmed that ABCG2 overexpression enhanced TNBC resistance to 2257 in vitro, while knockdown enhanced sensitivity. These findings suggest that 2257 is a substrate of ABCG2's drug efflux activity. However, overexpression of ABCG2 failed to confer resistance to 2257 in TNBC xenografts grown in mice and treated with a moderately active dose and schedule. Our results highlight the potential impact of drug transporters in in vitro CRISPR screens and the importance of confirming the relevance of drug response mechanisms identified in cultured cells using in vivo models that recapitulate drug pharmacokinetics and pharmacodynamics. - Source: PubMed
Publication date: 2026/03/14
Thu Kelsie LJafari SoodeSilvester JenniferCruickshank JenniferSoria-Bretones IsabelHodgson KelseyTobin ChantalHaight JillianLau Asa P YBray TessaWakeham DrewBray Mark RMak Tak WCescon David W - The outer kinetochore (KT) physically links chromosomes to dynamic microtubule (MT) plus ends, coupling to both polymerizing and depolymerizing tips to support chromosome movements while maintaining robust attachment. In human cells, the Ska complex is thought to function analogously to the yeast Dam1 complex and to cooperate with Ndc80 at the outer KT to ensure stable KT-MT interactions. However, the molecular basis for this cooperation remains poorly understood. We have obtained structures of human Ska and Ndc80 complexes simultaneously bound to MTs, showing how Ska interacts with MT across several tubulin dimers. Ndc80 and Ska complexes engage with each other across adjacent protofilaments "sandwiching" the α-tubulin C-terminal tail in the process. We also identify an anchoring interaction between a distinct bending point within the Ndc80 coiled-coil and a tethering helix and nearby phosphorylation sites (T358/T360) in SKA3. Our findings shed light on how human outer KT components collaboratively engage dynamic MT ends to contribute to robust KT-MT attachment and fidelity during chromosome segregation in mitosis. - Source: PubMed
Publication date: 2025/12/07
Zhou JuZhao YuanchangYildiz AhmetNogales Eva