PMID- 36291175
OWN - NLM
STAT- MEDLINE
DCOM- 20221028
LR  - 20221204
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 20
DP  - 2022 Oct 21
TI  - FAM57A (Family with Sequence Similarity 57 Member A) Is a Cell-Density-Regulated 
      Protein and Promotes the Proliferation and Migration of Cervical Cancer Cells.
LID - 10.3390/cells11203309 [doi]
LID - 3309
AB  - The 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 alpha-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.
FAU - Yang, Dongyun
AU  - Yang D
AUID- ORCID: 0000-0002-7325-7937
AD  - Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center 
      (DKFZ), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
FAU - Strobel, Tobias D
AU  - Strobel TD
AD  - Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center 
      (DKFZ), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
AD  - Faculty of Biosciences, Heidelberg University, D-69120 Heidelberg, Germany.
FAU - Bulkescher, Julia
AU  - Bulkescher J
AD  - Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center 
      (DKFZ), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
FAU - Tessmer, Claudia
AU  - Tessmer C
AD  - Genomics and Proteomics Core Facility, Unit Antibodies, German Cancer Research 
      Center (DKFZ), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
FAU - Hofmann, Ilse
AU  - Hofmann I
AD  - Genomics and Proteomics Core Facility, Unit Antibodies, German Cancer Research 
      Center (DKFZ), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
FAU - Hoppe-Seyler, Felix
AU  - Hoppe-Seyler F
AD  - Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center 
      (DKFZ), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
FAU - Hoppe-Seyler, Karin
AU  - Hoppe-Seyler K
AD  - Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center 
      (DKFZ), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221021
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Uterine Cervical Neoplasms/metabolism
MH  - *Oncogene Proteins, Viral/genetics/metabolism
MH  - Papillomavirus E7 Proteins/genetics/metabolism
MH  - *Papillomavirus Infections
MH  - Repressor Proteins/genetics/metabolism
MH  - Transcription Factors
MH  - Cell Proliferation
MH  - Hypoxia
MH  - Cell Count
MH  - RNA
PMC - PMC9600422
OTO - NOTNLM
OT  - FAM57A
OT  - cervical cancer
OT  - human papillomavirus (HPV)
OT  - hypoxia
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/10/28 06:00
MHDA- 2022/10/29 06:00
PMCR- 2022/10/21
CRDT- 2022/10/27 01:10
PHST- 2022/09/14 00:00 [received]
PHST- 2022/10/17 00:00 [revised]
PHST- 2022/10/17 00:00 [accepted]
PHST- 2022/10/27 01:10 [entrez]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2022/10/29 06:00 [medline]
PHST- 2022/10/21 00:00 [pmc-release]
AID - cells11203309 [pii]
AID - cells-11-03309 [pii]
AID - 10.3390/cells11203309 [doi]
PST - epublish
SO  - Cells. 2022 Oct 21;11(20):3309. doi: 10.3390/cells11203309.