The Specifically Androgen-Regulated Gene (SARG) Promotes Papillary Thyroid Carcinoma (PTC) Lymphatic Metastasis Through Vascular Endothelial Growth Factor C (VEGF-C) and VEGF Receptor 3 (VEGFR-3) Axis

Xu, Shuai-Jun; Jin, Bin; Zhao, Wenxuan; Chen, Xue‐Xian; Tong, Yuru; Ding, Xiaofei; Chen, Ying-Yuan; Wang, Dong-Hao; Wang, Zhiming; Dai, Bing-Qing; Chen, Sai; Liang, Yong; Chen, Guang; Pan, Su-Jiao; Xu, Linglong

doi:10.3389/fonc.2022.817660

Cited by 2 publications

(2 citation statements)

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“…When looking at our differential chromatography results, it becomes striking that no C. parvum proteins and only twenty-five host cell proteins are exclusively identified in the BKI-1748 column eluates. Two of them, Ladinin-1 and the SARG protein, both related to cancer formation [ 37 , 38 ], are commonly found in non-infected and infected host cell eluates, while twenty-two proteins are identified in infected HCT-8 eluates only. The by far most abundant of them is the protein S100-A2.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Targets of the 5-Amido-Carboxamide Bumped Kinase Inhibitor BKI-1748 in Cryptosporidium parvum and HCT-8 Host Cells

Ajiboye,

Uldry,

Heller

et al. 2024

IJMS

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Cryptosporidium parvum is an apicomplexan parasite causing persistent diarrhea in humans and animals. Issuing from target-based drug development, calcium-dependent protein kinase 1 inhibitors, collectively named bumped kinase inhibitors (BKIs), with excellent efficacies in vitro and in vivo have been generated. Some BKIs including BKI-1748 share a core structure with similarities to the first-generation antiprotozoal drug quinine, which is known to exert notorious side effects. Unlike quinine, BKI-1748 rapidly interfered with C. parvum proliferation in the human colon tumor (HCT) cell line HCT-8 cells and caused dramatic effects on the parasite ultrastructure. To identify putative BKI targets in C. parvum and in host cells, we performed differential affinity chromatography with cell-free extracts from non-infected and infected HCT-8 cells using BKI-1748 and quinine epoxy-activated sepharose columns followed by mass spectrometry. C. parvum proteins of interest were identified in eluates from columns coupled to BKI-1748, or in eluates from both BKI-1748 and quinine columns. However, no C. parvum proteins could be identified binding exclusively to BKI-1748. In contrast, 25 BKI-1748-specific binding proteins originating from HCT-8 cells were detected. Moreover, 29 C. parvum and 224 host cell proteins were identified in both BKI-1748 as well as in quinine eluates. In both C. parvum and host cells, the largest subset of binding proteins was involved in RNA binding and modification, with a focus on ribosomal proteins and proteins involved in RNA splicing. These findings extend previous results, showing that BKI-1748 interacts with putative targets involved in common, essential pathways such as translation and RNA processing.

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Section: Discussionmentioning

confidence: 99%

“…One is Ladinin-1, a basement membrane protein probably involved in lung cancer formation [37]. The other is the isoform 2 of a specifically androgen-regulated protein, a steroid responsive transcription factor involved in prostate cancer and thyroid cancer metastasis [38]. Table 3.…”

Section: Host Cell Proteins Identified By Dacmentioning

confidence: 99%