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
- During final cell division, the cleaved midbody is either released or asymmetrically retained as a midbody remnant (MBR). MBRs play critical roles in cell communication, signal transduction, and translation regulation, influencing cellular fate. Here, we synthesize their functions as RNA-processing granules, polarity regulators, and signaling platforms, emphasizing their role in primary cilia formation. In polarized epithelial cells, the MBR moves along the apical surface to the centrosome, delivering membrane components to permit ciliogenesis. In ductal carcinoma cells, MBR-localized Shc1-binding protein (SHCBP1) interacts with TBC1 domain family member 30 (TBC1D30 to antagonize Ras-related protein Rab-8 (Rab8) GTPase activity, blocking MBR-centrosome proximity and silencing ciliogenesis. Beyond ciliary regulation, MBRs integrate Wnt, PDGF, TGF-, and genomic stability networks, acting as dynamic signaling hubs during cancer development. Regarding therapeutic strategies targeting MBRs, High SHCBP1 expression correlates with ciliary loss and poor prognosis in breast, pancreatic, and cholangiocarcinoma. Targeting the SHCBP1/Rab8 axis to restore ciliogenesis by reestablishing MBR-centrosome proximity offers a potential therapeutic strategy. In addition, secreted MBRs are enriched in signaling components and transcripts, serving as intercellular carriers of oncogenic cargoes and promising liquid biopsy biomarkers. In summary, by tracing MBRs from their postmitotic origin to their pathogenic roles, we highlight vulnerabilities within MBR regulatory networks and provide novel insights for cancer therapeutics. - Source: PubMed
Publication date: 2026/05/04
Li HongbinMa XiaoliLiang JingXue KaiShi WenguiLang Wanying - Nonobstructive azoospermia (NOA) is one of the most severe types of male infertility. Amino acid metabolism (AAM) is strongly associated with various diseases. This study intended to identify biomarkers related to AAM in NOA. Biomarkers were screened from GSE9210, GSE108886, and AAM-related genes through a series of bioinformatics analyses. Then, the diagnostic efficacy of the biomarkers was evaluated. Furthermore, the mechanisms of action of these biomarkers were investigated through enrichment analysis, immune infiltration analysis, construction of regulatory networks, prediction of potential drugs, and prediction of related diseases. Finally, reverse transcription-quantitative polymerase chain reaction was performed for verification. Three biomarkers (AKT1, ASNS, and SHC1) were derived, which demonstrated good diagnostic efficacy for NOA. Meanwhile, AKT1, ASNS, and SHC1 might play significant roles in the development of male germ cells through pathways such as male gamete generation, sexual reproduction, and gamete generation. Immune infiltration analysis revealed these 3 biomarkers were closely associated with T follicular helper cells, resting natural killer cells, and regulatory T cells. And AKT1, ASNS, and SHC1 were regulated by 24 transcription factors and 15 microRNAs. Remarkably, sodium selenite, aflodac, and genistein were commonly predicted by the biomarkers. In addition, lung neoplasms were associated with AKT1, lipoidosis was associated with ASNS, and drug-induced acute liver injury was associated with SHC1. Ultimately, AKT1 and SHC1 were significantly upregulated in NOA. This study identified 3 biomarkers as being associated with NOA, providing valuable clues to help treat and predict NOA. - Source: PubMed
Guo Qing HuaDing Zhong JunLiu Dong MeiRen Xiao ShanChen XiaoYong - Plasma membrane (PM) ion transport depends on tightly regulated trafficking and activation of ion channels. For the cystic fibrosis transmembrane conductance regulator (CFTR), dysregulation caused by tobacco smoke or chronic inflammation contributes to diseases such as chronic obstructive pulmonary disease (COPD). We previously showed that phosphorylation of CFTR at tyrosine 512 (Y512) by spleen tyrosine kinase promotes its internalization via the MAPK/SHC-1 pathway in CFBE airway cells. Here, we investigated whether this mechanism is conserved in other epithelial models and whether inhibition of SHC-1 increased CFTR abundance at the PM. CFTR surface levels were assessed in CFBE, 16HBE, and Caco-2 cells using biotinylation and immunoblotting after treatment with MEK inhibitor selumetinib, SHC-1 inhibitor idebenone (IDE), or its novel inhibitor 110#3. MAPK activity was evaluated by ERK phosphorylation. We found that MAPK/SHC-1-dependent CFTR internalization was conserved in 16HBE and Caco-2 cells. In CFBE cells, treatment with IDE or 110#3 increased PM CFTR levels, but also unrelated PM proteins (GLUT1 and E-cadherin). No significant effects were observed in 16HBE or Caco-2 cells. These findings suggest CFBE cells may not fully recapitulate endogenous CFTR trafficking and raise the possibility that selective SHC-1/pY512-CFTR inhibitors may modulate CFTR trafficking in COPD and other CFTR-related diseases. - Source: PubMed
Publication date: 2026/04/13
Barros PatríciaPereira Mariana F LTomilov AlexeyCortopassi GinoJordan PeterMatos Paulo - Human epidermal growth factor receptor 2 (HER2)-tyrosine kinase inhibitors (TKIs) are being developed for the treatment of patients with HER2-aberrant lung and gastric cancers. However, achieving complete tumor remission remains challenging. Here, we investigated the molecular mechanisms underlying adaptive resistance to HER2-TKIs in HER2-aberrant tumor cells in order to devise strategies to prevent the emergence of drug-tolerant cells. Our findings showed that the AXL receptor was activated by HER2-TKIs and maintained cell survival by interacting with epidermal growth factor receptor, HER2, and HER3. This process, mediated by the SHC1BP-SHC1 axis, contributed to adaptive resistance to HER2-TKIs in a subset of HER2-aberrant lung and gastric cancers. AXL inhibition significantly delayed tumor regrowth of AXL-overexpressing cells by enhancing HER2-TKI-induced apoptosis in xenograft models. These results suggest that patients with HER2-aberrant lung and gastric cancers exhibiting high AXL expression may benefit from an initial combination therapy with an AXL inhibitor. - Source: PubMed
Publication date: 2026/04/02
Ishida MasakiYamada TadaakiKatayama YukiKawachi HayatoSawada RyoNakamura RyotaHirai SoichiMatsui YoheiMorimoto KenjiOnoi KeisukeNakamura-Sasada AosaHorinaka ManoSakai ToshiyukiSakakida TomokiDoi ToshifumiYasumoto KazuoGoto YasuhiroFuruya NaokiTaniguchi HirokazuOgino HirokazuTakayuki NakanoChihara YusukeFukuda KojiTaniguchi HiroakiUehara HisanoriYano SeijiTokuda ShinsakuTakayama Koichi - While epidermal growth factor receptor (EGFR) fusions in non-small cell lung cancer (NSCLC) typically show sensitivity to tyrosine kinase inhibitors (TKIs), we identified an EGFR-SHC1 fusion subtype that exhibits intrinsic resistance to EGFR-TKI monotherapy through a dual activation mechanism in the preclinical and clinical setting. EGFR-SHC1 fusion protein comprises of N-terminal EGFR and C-terminal SHC1. We demonstrated that EGFR-SHC1 simultaneously activates the EGFR kinase domain (KD) and SRC-mediated phosphorylation of the SHC1 fusion partner, thereby driving ERK/AKT pathway activation and tumorigenesis independent of KD inhibition. Structural modeling coupled with domain-specific mutagenesis revealed that SHC1 phosphorylation establishes a kinase-independent bypass mechanism. Notably, dual-targeted inhibition using afatinib (EGFR-TKI) in combination with dasatinib (SRC-TKI) induced marked tumor regression in a TKI-refractory NSCLC patient with EGFR-SHC1. This study illustrates a cooperative oncogenesis between kinase and scaffold protein in fusions, providing a clinically actionable strategy for overcoming TKI resistance in patients with these oncogenic fusions. - Source: PubMed
Publication date: 2026/03/24
Zheng JianiZhao ShenZhan JianhuaZhuang WeitaoChen MaojianJiang WeiHuang YihuaHe JunyiHu LiyangPang LanlanHao FengXue JinhuiShi MengtingLi AnlinWu JingxunHong ShaodongZhao YuanyuanYe FengHuang YanZhao HongyunYang YunpengFang WenfengZhang LiLi Jing