Çırçır, Ayça
Sorting nexin 3 (SNX3) is one of the sorting nexin family proteins and recruits the retromer complex in endosomal trafficking. SNX3 binds specifically to Phosphotidylinositol3Phosphate (PtdIns(3)P) via its Phox-domain (PX) domain but can also interact with cargo proteins which are mostly membrane receptors. Internalized receptors can be recycled back to the plasma membrane or the trans Golgi network or degraded in lysosomes or proteosomes. In addition to the role of SNX3 in Wntless (Wls) and Transferrin receptor (Tfrc) turnover, previous work and ours demonstrated the epidermal growth factor receptor (EGFR) as a recycling cargo of SNX3. Considering the critical role of EGFR in cell survival, proliferation, invasion/migration and clonogenicity of EGFR positive triple negative breast cancers (TNBCs), we hypothesized that SNX3 might modulate EGFR levels in TNBCs and deregulation of SNX3 might result in the alteration of clinical phenotypes. To experiment with our hypothesis, we generated Snx3 knockdown mouse mammary cell line models and evaluated the alterations in the neoplastic phenotypes of the cells. Early response to Snx3 downregulation decreased the Egfr protein, whereas extended silencing of Snx3 resulted in both Egfr protein and Egfr mRNA upregulation. Upregulation of the Egfr protein enhanced the phenotype of 4T1 cells to a more aggressive state. In summary, Snx3 levels are critical for Egfr protein levels. Our results suggest that Snx3 loss may explain Egfr overexpression cases in triple negative breast cancer patients who do not have genomic amplification.


Sorting nexin 3 (SNX3) is an immediate and sustained target of EGF stimulation in EGFR positive breast cells
Çiçek, Esra; Erson Bensan, Ayşe Elif; Department of Biology (2021-9-10)
Sorting nexin 3 (SNX3) is a member of the sorting nexins family, which is involved in the endocytic trafficking network. SNX3 only has a PX domain, which helps endosomes bind to phosphatidyl inositol-3-phosphate and plays a role in the constitution of the retromer complex on early endosomes. Endocytosed receptors are internalized and recycled back to the plasma membrane, the Trans-Golgi Network, or are degraded in the lysosomes. The current understanding of SNX3 function in recycling Epidermal Growth Factor...
Characterization of sorting nexin 3 (SNX3) function
Öyken, Merve; Bensan, A. Elif Erson.; Department of Biology (2020)
Sorting nexin 3 (SNX3) belongs to the sorting nexins family involved in endocytic trafficking network. SNX3 only has a PX domain, which facilitates binding to the phosphatidyl inositol-3-phosphate on endosomes and has a role in formation of the retromer complex on early endosomes. Endocytosed receptors go through internalization and recycle back to plasma membrane, Trans-Golgi Network or alternatively are degraded in the lysosomes. Earlier, we found that SNX3 messenger RNA (mRNA) is upregulated via alternat...
APOBEC3B expression in drug resistant MCF-7 breast cancer cell lines
Onguru, Onder; Yalcin, Serap; Rosemblit, Cinthia; Zhang, Paul J.; Kilic, Selim; Gündüz, Ufuk (2016-04-01)
APOBEC3B belongs to a protein family of cytidine deaminases that can insert mutations in DNA and RNA as a result of their ability to deaminate cytidine to uridine. It has been shown that APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers. We investigated APOBEC3B expression in four drug resistant breast cancer cell lines (Doxorubicin, Etoposide, Paclitaxel and Docetaxel resistant MCF-7 cell lines) using a novel RNA in situ hybridization technology (RNAscope) and compare...
Terzi Çizmecioğlu, Nihal(2016-12-31)
Sin3a korepresor kompleksi içindeki histon deasetilaz proteinlerinin sayesinde gen ekspresyonunu bastırma görevi olan bir kromatin kompleksidir. Yaptığımız çalışmalarda, embriyonik kök hücrelerin pluripotent yapısını kaybedip mezoderm ve endoderm tabakalarına farklılaşmasında Sin3a kompleksinin içinde yer alan Arid4b ve Hdac1 proteinlerinin kritik bir rol oynadığını bulduk. Arid4b veya Hdac1 proteinlerinden yoksun hücreler farklılaşma için gerekli transkripsiyon faktörlerini ve daha alt basamaklardaki efekt...
Investigating SNX3 binding motif on EGFR
Ercan, Melda; Erson Bensan, Ayşe Elif; Department of Molecular Biology and Genetics (2019)
Sorting Nexin 3 (SNX3) is a protein that is involved in retromer complex and has a role in recognition and trafficking of retromer cargo proteins. SNX3-retromer provides the recycling of their cargo proteins back to the plasma membrane or to Trans Golgi Network. Recent studies reveal the specificity of SNX3 in cargo recognition by acting on a recycling motif on receptor cytoplasmic tails. Considering the importance of SNX3 in receptor recycling, we hypothesized that EGFR can be one of the cargo proteins tha...
Citation Formats
A. Çırçır, “SNX3 LOSS ENHANCES EGFR OVEREXPRESSION IN A MOUSE TRIPLE NEGATIVE BREAST CANCER MODEL,” Ph.D. - Doctoral Program, Middle East Technical University, 2023.