PMID- 36500393
OWN - NLM
STAT- MEDLINE
DCOM- 20221216
LR  - 20221222
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 23
DP  - 2022 Nov 28
TI  - Investigating the Function of Human Jumping Translocation Breakpoint Protein 
      (hJTB) and Its Interacting Partners through In-Solution Proteomics of MCF7 Cells.
LID - 10.3390/molecules27238301 [doi]
LID - 8301
AB  - Human jumping translocation breakpoint (hJTB) gene is located on chromosome 1q21 
      and is involved in unbalanced translocation in many types of cancer. JTB protein 
      is ubiquitously present in normal cells but it is found to be overexpressed or 
      downregulated in various types of cancer cells, where this protein and its 
      isoforms promote mitochondrial dysfunction, resistance to apoptosis, genomic 
      instability, proliferation, invasion and metastasis. Hence, JTB could be a tumor 
      biomarker for different types of cancer, such as breast cancer (BC), and could be 
      used as a drug target for therapy. However, the functions of the protein or the 
      pathways through which it increases cell proliferation and invasiveness of cancer 
      cells are not well-known. Therefore, we aim to investigate the functions of JTB 
      by using in-solution digestion-based cellular proteomics of control and 
      upregulated and downregulated JTB protein in MCF7 breast cancer cell line, taking 
      account that in-solution digestion-based proteomics experiments are complementary 
      to the initial in-gel based ones. Proteomics analysis allows investigation of 
      protein dysregulation patterns that indicate the function of the protein and its 
      interacting partners, as well as the pathways and biological processes through 
      which it functions. We concluded that JTB dysregulation increases the 
      epithelial-mesenchymal transition (EMT) potential and cell proliferation, 
      harnessing cytoskeleton organization, apical junctional complex, metabolic 
      reprogramming, and cellular proteostasis. Deregulated JTB expression was found to 
      be associated with several proteins involved in mitochondrial organization and 
      function, oxidative stress (OS), apoptosis, and interferon alpha and gamma 
      signaling. Consistent and complementary to our previous results emerged by using 
      in-gel based proteomics of transfected MCF7 cells, JTB-related proteins that are 
      overexpressed in this experiment suggest the development of a more aggressive 
      phenotype and behavior for this luminal type A non-invasive/poor-invasive human 
      BC cell line that does not usually migrate or invade compared with the highly 
      metastatic MDA-MB-231 cells. This more aggressive phenotype of MCF7 cells related 
      to JTB dysregulation and detected by both in-gel and in-solution proteomics could 
      be promoted by synergistic upregulation of EMT, Mitotic spindle and Fatty acid 
      metabolism pathways. However, in both JTB dysregulated conditions, several 
      downregulated JTB-interacting proteins predominantly sustain antitumor 
      activities, attenuating some of the aggressive phenotypical and behavioral traits 
      promoted by the overexpressed JTB-related partners.
FAU - Jayathirtha, Madhuri
AU  - Jayathirtha M
AD  - Biochemistry & Proteomics Laboratories, Department of Chemistry and Biomolecular 
      Science, Clarkson University, Potsdam, NY 13699-5810, USA.
FAU - Whitham, Danielle
AU  - Whitham D
AD  - Biochemistry & Proteomics Laboratories, Department of Chemistry and Biomolecular 
      Science, Clarkson University, Potsdam, NY 13699-5810, USA.
FAU - Alwine, Shelby
AU  - Alwine S
AD  - Biochemistry & Proteomics Laboratories, Department of Chemistry and Biomolecular 
      Science, Clarkson University, Potsdam, NY 13699-5810, USA.
FAU - Donnelly, Mary
AU  - Donnelly M
AUID- ORCID: 0000-0002-9266-1580
AD  - Biochemistry & Proteomics Laboratories, Department of Chemistry and Biomolecular 
      Science, Clarkson University, Potsdam, NY 13699-5810, USA.
FAU - Neagu, Anca-Narcisa
AU  - Neagu AN
AD  - Laboratory of Animal Histology, Faculty of Biology, "AlexandruIoanCuza" 
      University of Iasi, Carol I bvd. No. 20A, 700505 Iasi, Romania.
FAU - Darie, Costel C
AU  - Darie CC
AUID- ORCID: 0000-0001-6402-2311
AD  - Biochemistry & Proteomics Laboratories, Department of Chemistry and Biomolecular 
      Science, Clarkson University, Potsdam, NY 13699-5810, USA.
LA  - eng
GR  - R15CA260126/National Cancer Institute, National Institutes of Health/
PT  - Journal Article
DEP - 20221128
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
SB  - IM
MH  - Humans
MH  - Female
MH  - MCF-7 Cells
MH  - *Proteomics/methods
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Apoptosis/genetics
MH  - Cell Proliferation
MH  - *Breast Neoplasms/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Neoplasm Invasiveness
PMC - PMC9740069
OTO - NOTNLM
OT  - EMT
OT  - MCF7
OT  - breast cancer
OT  - in-solution proteomics
OT  - jumping translocation breakpoint (JTB) protein
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/12 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/11/28
CRDT- 2022/12/11 01:27
PHST- 2022/09/20 00:00 [received]
PHST- 2022/11/16 00:00 [revised]
PHST- 2022/11/16 00:00 [accepted]
PHST- 2022/12/11 01:27 [entrez]
PHST- 2022/12/12 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/11/28 00:00 [pmc-release]
AID - molecules27238301 [pii]
AID - molecules-27-08301 [pii]
AID - 10.3390/molecules27238301 [doi]
PST - epublish
SO  - Molecules. 2022 Nov 28;27(23):8301. doi: 10.3390/molecules27238301.