Ask about this productRelated genes to: Shc1 antibody
- Gene:
- SHC1 NIH gene
- Name:
- SHC adaptor protein 1
- Previous symbol:
- SHC
- Synonyms:
- p66, ShcA
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-02-17
- Date modifiied:
- 2016-10-05
Related products to: Shc1 antibody
Related articles to: Shc1 antibody
- Understanding the mechanisms of metastasis is one of the most pressing issues in cancer therapy. Metastasis-associated in colon cancer 1 (MACC1) is an important biomarker and functional driver of tumor progression and metastasis. However, the molecular mechanisms underlying its activity remain incompletely understood. Here, we demonstrate that MACC1 acts as an important adaptor protein that promotes hyperactivation of receptor tyrosine kinase (RTK) signaling pathways in colorectal cancer (CRC) cells. Based on mass spectrometry-based interactomics, we identified key MACC1 interactors, including GRB2, SHP2, SHC1, and STAT5B, that preferentially associate with tyrosine-phosphorylated residues Y365, Y379, and Y789. Site-directed mutagenesis of Y379 and Y789 reduced MACC1-induced migration, proliferation, and ERK phosphorylation. Using digital Western blotting (DigiWest), we observed a broad MACC1-dependent hyperactivation of downstream signaling effectors, including MEK, ERK, β-catenin, SRC, FAK, CREB, and VASP. Targeting MACC1-induced signaling with clinically relevant inhibitors effectively reversed MACC1-driven clonogenicity. Our findings support a role for MACC1 in promoting hyperactivation of RTK-associated signaling and reveal pharmacological vulnerabilities of potential relevance to metastasis-prone cancers characterized by elevated MACC1 expression. - Source: PubMed
Publication date: 2026/09/02
Zincke FabianKobelt DennisKläger SusanPachl FionaErdmann GerritDahlmann MathiasWalther WolfgangKüster BernhardStein Ulrike - Vaginal atrophy (VA), a common condition associated with oestrogen deficiency, significantly impacts women's quality of life. Src homology 2 domain-containing transforming protein 1 (SHC1) is implicated in various hormone-dependent processes. This project aims to investigate whether oestrogen promotes the proliferation, migration and differentiation of vaginal epithelial cells by regulating SHC1, and delineates the underlying mechanism. - Source: PubMed
Publication date: 2026/09/23
Li JingLi JuanMou DarongLi Dongyan - Integrated single-cell transcriptomics and clinical analyses reveal elevated DDR1 expression in pancreatic ductal adenocarcinoma (PDAC) tissues, which correlates with poor prognosis. Mechanistically, collagen-activated Discoidin Domain Receptor 1 (DDR1) recruits SHC1 to activate the MAPK/ERK pathway, thereby driving transcriptional upregulation of SLC40A1 via the ERK-MYC axis. SLC40A1, encoding an iron exporter, reduces intracellular labile iron pools, thereby suppressing lipid peroxidation and ferroptosis. Consequently, DDR1 overexpression confers resistance to dihydroartemisinin (DHA)-induced ferroptosis in PDAC cells, characterized by diminished ROS accumulation, mitochondrial shrinkage, and cristae loss. Conversely, DDR1 knockdown or pharmacological inhibition (Dasatinib) sensitizes PDAC cells to DHA. Crucially, combining Dasatinib and DHA treatment synergistically inhibits tumor growth in vivo by reactivating ferroptosis, as evidenced by increased 4-HNE accumulation and decreased Ki67 expression. These findings identify DDR1 as a key regulator of iron metabolism and ferroptosis in PDAC, suggesting that dual targeting of DDR1 and ferroptosis represents a promising therapeutic strategy. - Source: PubMed
Publication date: 2026/09/23
Song ChaoZhang LutingXu ShengWang Xu-AnZhang XinyiCheong Kai XuanWang GanggangLiu MengmengWang YazhouZhang YifeiHe TaochenDing KaiChen YuLiang XinZhu BingNi QianzhiWang WenquanLi JingjingLou WenhuiLiu Liang - Histone deacetylase 8 (HDAC8) is a promising therapeutic target in cancer; however, the clinically approved hydroxamate-based inhibitors exhibit weak selectivity and undesirable toxicity due to binding at multiple sites. In this work, we report the design and synthesis of a new class of non-hydroxamate HDAC8 inhibitors with an unexplored cyanocarbonimidodithioate zinc-binding group (ZBG). A series of new compounds (SHC 1-3 and AC 1-14) were synthesized by the optimization of the cap groups and linker. SHC-1 and SHC-2 were found to be the most potent and selective HDAC8 inhibitors, with IC values of 0.036 μM and 0.041 μM, respectively, and high selectivity for HDAC8 over other HDAC isoforms. SHC-1 showed promising antiproliferative activity in IMR-32 neuroblastoma cells, colony formation inhibition, cell migration inhibition, caspase 3/7 assay and western blot. Mechanistic studies indicated increased SMC3 acetylation, suggesting HDAC8 inhibition. Molecular docking, molecular dynamics simulation, and MM-GBSA showed that SHC-2 binds stably to the HDAC8 active pocket via strong zinc coordination and critical interactions in the enzyme sub-pocket. ADMET predictions indicated good drug-likeness for the new compounds. A crystal of AC-4 was grown, and the structure was confirmed through SC-XRD. In summary, we have developed cyanocarbonimidodithioates as a new non-hydroxamate ZBG. These inhibitors demonstrated encouraging activity and a robust association with reported phenotypic changes, suggesting they could be further developed as cancer therapeutic agents. - Source: PubMed
Publication date: 2026/09/17
Kosana Sai ChaitanyaChaudhari HrushikeshFathima AshnaSengar SuryanshSchweipert MarkusKhetmalis Yogesh MahaduBandaru N V M RaoAbbineni ChandrasekharJamma TrinathSharma VivekMeyer-Almes Franz-JosefKondapalli Venkata Gowri Chandra Sekhar - is a major opportunistic fungal pathogen, and increasing azole resistance poses a challenge for aspergillosis treatment. Squalene is an upstream precursor of ergosterol biosynthesis and may also be utilized by SHC-like triterpene cyclases, suggesting a potential link between squalene-associated metabolism, membrane adaptation, and azole response. However, the roles of SHC-like triterpene cyclase genes in remain unclear. Here, we characterized three candidates, , , and , using comparative bioinformatic analysis, gene deletion, phenotypic assays, azole susceptibility testing, transcriptomics, and host-interaction models. Sequence, genomic-context, phylogenetic, and structural analyses suggested divergence among the three candidates. Individual deletion caused limited effects on vegetative growth, whereas loss of mildly reduced susceptibility to voriconazole and posaconazole, as reflected by twofold MIC increases and lower inhibition rates. Transcriptomic analysis revealed distinct remodeling patterns, with showing the broadest transcriptional changes despite no detectable MIC shift. Targeted metabolite profiling and PI uptake analysis further supported an association between deletion, sterol/hopane-type triterpenoid balance, and membrane-associated properties. deletion also altered epithelial cell interaction phenotypes, while Δ showed reduced lethality in . In clinical isolates, elevated transcription was associated with azole-resistant backgrounds. These findings suggest functional diversification among SHC-like triterpene cyclase genes and indicate that may contribute to azole-associated adaptation and virulence-related traits in . - Source: PubMed
Publication date: 2026/09/05
Ye KeruiChen FangyanHu LingxueHan JinghuiLi DingchenHu MandongWang ChangjunZeng JumeiHan Li