Dergi makalesi Açık Erişim
Cicek, Esra; Circir, Ayca; Oyken, Merve; Caliskan, Ozge Akbulut; Dioken, Didem Naz; Ergun, Sezen Guntekin; Cetin-Atalay, Rengul; Sapmaz, Aysegul; Ovaa, Huib; Sahin, Ozgur; Erson-Bensan, Ayse Elif
<?xml version='1.0' encoding='UTF-8'?> <record xmlns="http://www.loc.gov/MARC21/slim"> <leader>00000nam##2200000uu#4500</leader> <datafield tag="245" ind1=" " ind2=" "> <subfield code="a">EGF-SNX3-EGFR axis drives tumor progression and metastasis in triple-negative breast cancers</subfield> </datafield> <datafield tag="909" ind1="C" ind2="4"> <subfield code="p">ONCOGENE</subfield> <subfield code="v">41</subfield> <subfield code="n">2</subfield> <subfield code="c">220-232</subfield> </datafield> <controlfield tag="001">237572</controlfield> <datafield tag="980" ind1=" " ind2=" "> <subfield code="a">user-tubitak-destekli-proje-yayinlari</subfield> </datafield> <datafield tag="520" ind1=" " ind2=" "> <subfield code="a">Epidermal growth factor receptor (EGFR) has critical roles in epithelial cell physiology. Over-expression and over-activation of EGFR have been implicated in diverse cancers, including triple-negative breast cancers (TNBCs), prompting anti-EGFR therapies. Therefore, developing potent therapies and addressing the inevitable drug resistance mechanisms necessitates deciphering of EGFR related networks. Here, we describe Sorting Nexin 3 (SNX3), a member of the recycling retromer complex, as a critical player in the epidermal growth factor (EGF) stimulated EGFR network in TNBCs. We show that SNX3 is an immediate and sustained target of EGF stimulation initially at the protein level and later at the transcriptional level, causing increased SNX3 abundance. Using a proximity labeling approach, we observed increased interaction of SNX3 and EGFR upon EGF stimulation. We also detected colocalization of SNX3 with early endosomes and endocytosed EGF. Moreover, we show that EGFR protein levels are sensitive to SNX3 loss. Transient RNAi models of SNX3 downregulation have a temporary reduction in EGFR levels. In contrast, long-term silencing forces cells to recover and overexpress EGFR mRNA and protein, resulting in increased proliferation, colony formation, migration, invasion in TNBC cells, and increased tumor growth and metastasis in syngeneic models. Consistent with these results, low SNX3 and high EGFR mRNA levels correlate with poor relapse-free survival in breast cancer patients. Overall, our results suggest that SNX3 is a critical player in the EGFR network in TNBCs with implications for other cancers dependent on EGFR activity.</subfield> </datafield> <datafield tag="650" ind1="1" ind2="7"> <subfield code="2">opendefinition.org</subfield> <subfield code="a">cc-by</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="u">Middle East Tech Univ METU, Dept Biol Sci, Dumlupinar Blv 1,Universiteler Mah, TR-06800 Ankara, Turkey</subfield> <subfield code="a">Circir, Ayca</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Oyken, Merve</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="u">Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey</subfield> <subfield code="a">Caliskan, Ozge Akbulut</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="u">Middle East Tech Univ METU, Dept Biol Sci, Dumlupinar Blv 1,Universiteler Mah, TR-06800 Ankara, Turkey</subfield> <subfield code="a">Dioken, Didem Naz</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="u">Middle East Tech Univ, Grad Sch Informat, Canc Syst Biol Lab, CanSyL, TR-06800 Ankara, Turkey</subfield> <subfield code="a">Ergun, Sezen Guntekin</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="u">Middle East Tech Univ, Grad Sch Informat, Canc Syst Biol Lab, CanSyL, TR-06800 Ankara, Turkey</subfield> <subfield code="a">Cetin-Atalay, Rengul</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Sapmaz, Aysegul</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Ovaa, Huib</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="u">Univ South Carolina, Coll Pharm, Drug Discovery & Biomed Sci, Columbia, SC 29208 USA</subfield> <subfield code="a">Sahin, Ozgur</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Erson-Bensan, Ayse Elif</subfield> </datafield> <datafield tag="980" ind1=" " ind2=" "> <subfield code="b">article</subfield> <subfield code="a">publication</subfield> </datafield> <datafield tag="542" ind1=" " ind2=" "> <subfield code="l">open</subfield> </datafield> <datafield tag="100" ind1=" " ind2=" "> <subfield code="u">Middle East Tech Univ METU, Dept Biol Sci, Dumlupinar Blv 1,Universiteler Mah, TR-06800 Ankara, Turkey</subfield> <subfield code="a">Cicek, Esra</subfield> </datafield> <datafield tag="260" ind1=" " ind2=" "> <subfield code="c">2022-01-01</subfield> </datafield> <controlfield tag="005">20221007095801.0</controlfield> <datafield tag="909" ind1="C" ind2="O"> <subfield code="o">oai:aperta.ulakbim.gov.tr:237572</subfield> <subfield code="p">user-tubitak-destekli-proje-yayinlari</subfield> </datafield> <datafield tag="856" ind1="4" ind2=" "> <subfield code="z">md5:62c65f9318e870b70a7895d9a36a4cd1</subfield> <subfield code="s">267</subfield> <subfield code="u">https://aperta.ulakbim.gov.trrecord/237572/files/bib-3f3d1456-c9c6-4240-85d0-60dc7f66e4d0.txt</subfield> </datafield> <datafield tag="540" ind1=" " ind2=" "> <subfield code="u">http://www.opendefinition.org/licenses/cc-by</subfield> <subfield code="a">Creative Commons Attribution</subfield> </datafield> <datafield tag="024" ind1=" " ind2=" "> <subfield code="a">10.1038/s41388-021-02086-9</subfield> <subfield code="2">doi</subfield> </datafield> </record>
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