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000182311 041__ $$aEnglish
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000182311 1001_ $$0P:(DE-He78)81bbcd4c5033f7ddd69eebd3be349e7e$$aYang, Dongyun$$b0$$eFirst author$$udkfz
000182311 245__ $$aFAM57A (Family with Sequence Similarity 57 Member A) Is a Cell-Density-Regulated Protein and Promotes the Proliferation and Migration of Cervical Cancer Cells.
000182311 260__ $$aBasel$$bMDPI$$c2022
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000182311 520__ $$aThe FAM57A (family with sequence similarity 57 member A) gene is controversially discussed to possess pro- or anti-tumorigenic potential. Here, we analyze the regulation of cellular FAM57A protein levels and study the functional role of FAM57A in HPV-positive cervical cancer cells. We find that FAM57A protein expression strongly depends on cell density, with FAM57A being readily detectable at low cell density, but undetectable at high cell density. This regulation occurs post-transcriptionally and is not mirrored by corresponding changes at the RNA level. We further show that FAM57A protein levels are highly increased in cervical cancer cells cultivated at hypoxia compared to normoxia and provide evidence that FAM57A is a hypoxia-responsive gene under control of the α-subunit of the HIF-1 (hypoxia-inducible factor-1) transcription factor. Yet, the strong relative increase of FAM57A protein levels in hypoxic cells is predominantly cell-density-dependent and occurs post-transcriptionally. Other anti-proliferative effectors besides hypoxia, such as silencing of HPV E6/E7 oncogene expression in cervical cancer cells, also result in an increase of FAM57A levels compared to untreated cells. Functional analyses reveal that FAM57A repression leads to pronounced anti-proliferative as well as anti-migratory effects in cervical cancer cells. Taken together, these results provide insights into the regulation of FAM57A protein levels and reveal that they underlie a tight cell-density-dependent control. Moreover, they identify FAM57A as a critical determinant for the phenotype of cervical cancer cells, which promotes their proliferation and migration capacities.
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000182311 650_7 $$2Other$$aFAM57A
000182311 650_7 $$2Other$$acervical cancer
000182311 650_7 $$2Other$$ahuman papillomavirus (HPV)
000182311 650_7 $$2Other$$ahypoxia
000182311 650_7 $$2NLM Chemicals$$aOncogene Proteins, Viral
000182311 650_7 $$2NLM Chemicals$$aPapillomavirus E7 Proteins
000182311 650_7 $$2NLM Chemicals$$aRepressor Proteins
000182311 650_7 $$2NLM Chemicals$$aTranscription Factors
000182311 650_7 $$063231-63-0$$2NLM Chemicals$$aRNA
000182311 650_2 $$2MeSH$$aHumans
000182311 650_2 $$2MeSH$$aFemale
000182311 650_2 $$2MeSH$$aUterine Cervical Neoplasms: metabolism
000182311 650_2 $$2MeSH$$aOncogene Proteins, Viral: genetics
000182311 650_2 $$2MeSH$$aOncogene Proteins, Viral: metabolism
000182311 650_2 $$2MeSH$$aPapillomavirus E7 Proteins: genetics
000182311 650_2 $$2MeSH$$aPapillomavirus E7 Proteins: metabolism
000182311 650_2 $$2MeSH$$aPapillomavirus Infections
000182311 650_2 $$2MeSH$$aRepressor Proteins: genetics
000182311 650_2 $$2MeSH$$aRepressor Proteins: metabolism
000182311 650_2 $$2MeSH$$aTranscription Factors
000182311 650_2 $$2MeSH$$aCell Proliferation
000182311 650_2 $$2MeSH$$aHypoxia
000182311 650_2 $$2MeSH$$aCell Count
000182311 650_2 $$2MeSH$$aRNA
000182311 7001_ $$0P:(DE-He78)0dd31e782183886a3a3728cd5a97194d$$aStrobel, Tobias D$$b1$$udkfz
000182311 7001_ $$0P:(DE-He78)c04ec6ab9480d74da506d656185ec7d2$$aBulkescher, Julia$$b2$$udkfz
000182311 7001_ $$0P:(DE-He78)44a33c775d0e27db79f8fd9e97a99e0a$$aTessmer, Claudia$$b3$$udkfz
000182311 7001_ $$0P:(DE-He78)0c4543046185361a644540fee0dad8b1$$aHofmann, Ilse$$b4$$udkfz
000182311 7001_ $$0P:(DE-He78)25779f8829ab7a7650e85a4cc871e6ac$$aHoppe-Seyler, Felix$$b5$$udkfz
000182311 7001_ $$0P:(DE-He78)97468f1980416a4376b44e701d25f24b$$aHoppe-Seyler, Karin$$b6$$eLast author$$udkfz
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