PMID- 36275363
OWN - NLM
STAT- MEDLINE
DCOM- 20230731
LR  - 20230731
IS  - 2767-9764 (Electronic)
IS  - 2767-9764 (Linking)
VI  - 2
IP  - 10
DP  - 2022 Oct
TI  - STAG2 expression is associated with adverse survival outcomes and regulates cell 
      phenotype in muscle-invasive bladder cancer.
PG  - 1129-1143
LID - 10.1158/2767-9764.crc-22-0155 [doi]
AB  - STAG2 (Stromal Antigen 2), in healthy somatic cells, functions in sister 
      chromatid cohesion, DNA damage repair, and genome organization, but its role in 
      muscle invasive bladder cancer (MIBC) remains unknown. Here, using whole-exome 
      and targeted sequencing (n=119 bladder cancer clinical samples), we found several 
      STAG2 mutations in MIBC that correlate with loss of protein expression. The 
      analysis of a bladder cancer tissue microarray (n=346) revealed that decreased 
      STAG2 protein expression is associated with improved overall and progression-free 
      survival for MIBC patients. In mouse xenograft studies, STAG2 knockdown (KD) 
      decelerated MIBC tumor growth, whereas STAG2 overexpression accelerated tumor 
      growth. In cell line studies, STAG2 loss augmented treatment with cisplatin, a 
      first-line therapy for MIBC. STAG2 KD or overexpression did not alter degree of 
      aneuploidy, copy number variations, or cell cycle distribution. However, unbiased 
      RNA sequencing analysis revealed that STAG2 KD altered gene expression. STAG2 KD 
      led to significant downregulation of several gene sets, such as collagen 
      containing extracellular matrix, external encapsulating structure organization, 
      and regulation of chemotaxis. Therefore, we investigated the effect of STAG2 KD 
      on cell migration and invasion in vitro. We found that STAG2 KD minimized cell 
      speed, displacement, and invasion. Altogether, our results present a 
      non-canonical function of STAG2 in promoting cell motility and invasion of MIBC 
      cells. This work forms the basis for additional investigation into the role of 
      STAG2 in transcriptional regulation and how it becomes dysregulated in 
      STAG2-mutant MIBC.
FAU - Athans, Sarah
AU  - Athans S
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
FAU - Krishnan, Nithya
AU  - Krishnan N
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
FAU - Ramakrishnan, Swathi
AU  - Ramakrishnan S
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
FAU - Cortes Gomez, Eduardo
AU  - Cortes Gomez E
AD  - Department of Bioinformatics and Biostatistics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
FAU - Lage-Vickers, Sofia
AU  - Lage-Vickers S
AD  - University of Buenos Aires, Buenos Aires, C1053 CABA, Argentina.
FAU - Rak, Monika
AU  - Rak M
AD  - Department of Cell Biology, Jagiellonian University, 31-007, Krakow, Poland.
FAU - Kazmierczak, Zara
AU  - Kazmierczak Z
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
FAU - Ohm, Joyce
AU  - Ohm J
AD  - Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
FAU - Attwood, Kristopher
AU  - Attwood K
AD  - Department of Bioinformatics and Biostatistics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
FAU - Wang, Jianmin
AU  - Wang J
AD  - Department of Bioinformatics and Biostatistics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
FAU - Woloszynska, Anna
AU  - Woloszynska A
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, 14203.
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221006
PL  - United States
TA  - Cancer Res Commun
JT  - Cancer research communications
JID - 9918281580506676
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Antigens, Nuclear)
RN  - 0 (STAG2 protein, human)
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *DNA Copy Number Variations
MH  - Cell Cycle Proteins/genetics
MH  - Antigens, Nuclear/genetics
MH  - *Urinary Bladder Neoplasms/genetics
MH  - Chromosome Segregation
MH  - Phenotype
MH  - Muscles/metabolism
PMC - PMC9583756
MID - NIHMS1835157
COIS- Conflict of Interest Statement The authors declare no potential conflicts of 
      interest.
EDAT- 2022/10/25 06:00
MHDA- 2022/10/25 06:01
PMCR- 2022/10/06
CRDT- 2022/10/24 03:56
PHST- 2022/10/24 03:56 [entrez]
PHST- 2022/10/25 06:00 [pubmed]
PHST- 2022/10/25 06:01 [medline]
PHST- 2022/10/06 00:00 [pmc-release]
AID - CRC-22-0155 [pii]
AID - 10.1158/2767-9764.crc-22-0155 [doi]
PST - ppublish
SO  - Cancer Res Commun. 2022 Oct;2(10):1129-1143. doi: 10.1158/2767-9764.crc-22-0155. 
      Epub 2022 Oct 6.