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Familial Testicular Germ Cell Tumor
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The SPRY4 gene on chromosome 5 encodes an inhibitor of the mitogen-activated protein kinase (MAPK) pathway, which is activated by the KITLG–KIT pathway. SPRY4 has been shown to increase methylation of the maternal allele promoter in TGCT patients, and a reduced expression of SPRY4 may lead to enhanced survival of abnormal PGC. On the other hand, the BAK1 (BCL2-antagonist/killer 1) gene on chromosome 6 encodes a pro-apoptotic protein that controls the death of mislocalized PGC during migration, and its activity is repressed by the KITLG–KIT pathway.
Gastrointestinal Stromal Tumors: From Molecular Pathogenesis to Therapy
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Joaquina Baranda, Stafinur Atay, Andrew K. Godwin
Frolov and colleagues in 2003 were the first to identify genetic markers that could predict the response of patients with metastatic/recurrent GIST to imatinib using multiple cell lines and clinical trial samples [166]. They hypothesized that by evaluating gene expression profiles in treated GIST cells and then utilizing these data to evaluate specimens from GIST patients taken before and after imatinib therapy (CSTI571-B2222 clinical trial), they would identify novel genetic biomarkers of this therapy and subsequently define additional downstream mediators of response. A total of 148 genes or ESTs were found to be differentially regulated; while 7 genes displayed a durable response following imatinib treatment, i.e., SPRY4A, FZD8, PDE2A, RTP801, FLJ20898, ARHGEF2 were downregulated, and MAFbx was upregulated. Interestingly, independent studies by Atay and colleagues which evaluated GIST-derived exosomes in the circulation found that SPRY4 protein levels in exosomes was associated with response to therapy [167]. Their studies also confirmed that both AKT- and ERK1/2-signaling pathways are rapidly inhibited after exposure to imatinib, but suggested that other signaling pathways may also be affected by imatinib treatment, which were further defined in subsequent studies [168, 169]. Expanding these studies, Rink and colleagues directly assessed pre-treatment biopsy samples from a prospective neoadjuvant phase II trial (RTOG 0132) and identified an expanded 38-gene signature that included 18 KRAB-ZNF 91 subfamily members, 10 of which mapped to a single locus on chromosome 19p [170]. siRNA synthetic lethal screens demonstrated that members of this gene signature may not only have predictive value, but functional relevance to enhance imatinib activity.
SPRY1 promotes cell proliferation and inhibits apoptosis by activating Hedgehog pathway in acute myeloid leukemia
Published in Hematology, 2022
Guiyang Lv, Yuanyuan Wang, ChunXiao Ji, Chunlei Shi, Ying Li
Sprouty (SPRY) family consists of four members (SPRY1, SPRY2, SPRY3 and SPRY4), which differs in tissue distribution, activity and interaction partners [4]. Growing evidence has demonstrated that SPRY1 plays an important role in cell proliferation, differentiation, migration and apoptosis [5]. SPRY1 is reported to be involved in the development of different types of cancers, such as ovarian cancer [6,7], gastric cancer [8], glioma [9] and breast cancer [5]. Additionally, the analysis of the Cancer Genome Atlas (TCGA) confirms that SPRY1 expression is significantly upregulated in patients with AML. However, none of the studies report on the effects of SPRY1 in AML to date.
Isolation and molecular characterization of spermatogonia from male Sprague-Dawley rats exposed in utero and postnatally to dibutyl phthalate or acrylamide
Published in Toxicology Mechanisms and Methods, 2019
Nathália P. Souza, Lora L. Arnold, Karen L. Pennington, Merielen G. Nascimento e Pontes, Helio A. Miot, João Lauro V. de Camargo, Samuel M. Cohen
A common mechanism used to set up negative-feedback loops is the inducible expression of inhibitor signaling pathways through the same signaling pathways that they end up controlling. Spry4 proteins can antagonize receptor tyrosine kinase (RTK) signaling participating in the negative-feedback control. Spry4 expression is involved in diverse cellular functions, including anti-proliferative activity, inhibition of migration, and promotion of differentiation, and survival (Kim and Bar-Sagi 2004; Mason et al. 2006; Felfly and Klein 2013).
New insight into the role of long non-coding RNAs in the pathogenesis of preeclampsia
Published in Hypertension in Pregnancy, 2019
Mohammad-Taher Moradi, Zohreh Rahimi, Asad Vaisi-Raygani
The SPRY4-IT1 lncRNA (NR_131221.1), which is located on human chromosome 5q31.3, is derived from an intronic region within the SPRY4 gene (52). It has been reported that the SPRY4-IT1 plays a role in apoptosis, migration, and invasion in melanoma (52). Zou et al. reported increased SPRY4-IT1 expression in the placenta of severe PE. Also, the SPRY4-IT1 might modulate cell proliferation, migration, and apoptosis in trophoblast cells (53).