PMID- 38285610
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240417
IS  - 1756-591X (Electronic)
IS  - 1756-5901 (Linking)
VI  - 16
IP  - 2
DP  - 2024 Feb 7
TI  - Single nucleotide polymorphisms and Zn transport by ZIP11 shape functional 
      phenotypes of HeLa cells.
LID - mfae006 [pii]
LID - 10.1093/mtomcs/mfae006 [doi]
AB  - Zinc (Zn) is a vital micronutrient with essential roles in biological processes 
      like enzyme function, gene expression, and cell signaling. Disruptions in the 
      cellular regulation of Zn2+ ions often lead to pathological states. Mammalian Zn 
      transporters, such as ZIP11, play a key role in homeostasis of this ion. ZIP11 
      resides predominately in the nucleus and Golgi apparatus. Our laboratory reported 
      a function of ZIP11 in maintaining nuclear Zn levels in HeLa cervical cancer 
      cells. Analyses of cervical and ovarian cancer patients' datasets identified four 
      coding, single nucleotide polymorphisms (SNPs) in SLC39A11, the gene that encodes 
      ZIP11, correlating with disease severity. We hypothesized that these SNPs might 
      translate to functional changes in the ZIP11 protein by modifying access to 
      substrate availability. We also proposed that a metal-binding site (MBS) in ZIP11 
      is crucial for transmembrane Zn2+ transport and required for maintenance of 
      various pathogenic phenotypes observed in HeLa cells. Here, we investigated these 
      claims by re-introducing single the SLC39A11 gene encoding for mutant residues 
      associated with the SNPs, as well as MBS mutations into HeLa cells knocked down 
      for the transporter. Some SNPs-encoding ZIP11 variants rescued Zn levels, 
      proliferation, migration, and invasiveness of knockdown (KD) cells. Conversely, 
      single MBS mutations mimicked the traits of KD cells, confirming the 
      transporter's role in establishing and maintaining proliferative, migratory, and 
      invasive traits. Overall, the intricate role of Zn in cellular dynamics and 
      cancer progression underscores the significance of Zn transporters like ZIP11 in 
      potential therapeutic interventions.
CI  - (c) The Author(s) 2024. Published by Oxford University Press.
FAU - Kim, Elizabeth Y
AU  - Kim EY
AUID- ORCID: 0009-0000-2292-9302
AD  - Department of Molecular Biology & Biochemistry, Wesleyan University, 52 Lawn 
      Ave., Middletown, CT 06459, USA.
FAU - Verdejo-Torres, Odette
AU  - Verdejo-Torres O
AUID- ORCID: 0009-0006-6955-5428
AD  - Department of Molecular Biology & Biochemistry, Wesleyan University, 52 Lawn 
      Ave., Middletown, CT 06459, USA.
FAU - Diaz-Rodriguez, Karla
AU  - Diaz-Rodriguez K
AUID- ORCID: 0000-0003-2329-7567
AD  - Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 60 
      Prescott St., Worcester, MA 01605, USA.
FAU - Hasanain, Farah
AU  - Hasanain F
AUID- ORCID: 0009-0007-8009-1633
AD  - Department of Molecular Biology & Biochemistry, Wesleyan University, 52 Lawn 
      Ave., Middletown, CT 06459, USA.
FAU - Caromile, Leslie
AU  - Caromile L
AUID- ORCID: 0000-0003-2193-5190
AD  - Departmentof Cell Biology, Center for Vascular Biology, UCONN Health-Center, 
      Farmington, CT 06030, USA.
FAU - Padilla-Benavides, Teresita
AU  - Padilla-Benavides T
AUID- ORCID: 0000-0002-4624-0822
AD  - Department of Molecular Biology & Biochemistry, Wesleyan University, 52 Lawn 
      Ave., Middletown, CT 06459, USA.
LA  - eng
GR  - Wesleyan University/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Metallomics
JT  - Metallomics : integrated biometal science
JID - 101478346
RN  - 0 (Membrane Transport Proteins)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Polymorphism, Single Nucleotide
MH  - HeLa Cells
MH  - *Membrane Transport Proteins
MH  - Phenotype
MH  - Zinc/metabolism
MH  - Mammals/metabolism
OTO - NOTNLM
OT  - ZIP11
OT  - metal binding
OT  - proliferation
OT  - single nucleotide polymorphisms
OT  - zinc
EDAT- 2024/01/29 19:57
MHDA- 2024/02/14 12:47
CRDT- 2024/01/29 12:43
PHST- 2023/08/13 00:00 [received]
PHST- 2024/01/27 00:00 [accepted]
PHST- 2024/02/14 12:47 [medline]
PHST- 2024/01/29 19:57 [pubmed]
PHST- 2024/01/29 12:43 [entrez]
AID - 7591316 [pii]
AID - 10.1093/mtomcs/mfae006 [doi]
PST - ppublish
SO  - Metallomics. 2024 Feb 7;16(2):mfae006. doi: 10.1093/mtomcs/mfae006.