PMID- 28657426
OWN - NLM
STAT- MEDLINE
DCOM- 20200409
LR  - 20200409
IS  - 2154-1256 (Electronic)
IS  - 2154-1248 (Print)
IS  - 2154-1248 (Linking)
VI  - 10
IP  - 5
DP  - 2019 Sep
TI  - Oncogenic Ect2 signaling regulates rRNA synthesis in NSCLC.
PG  - 388-394
LID - 10.1080/21541248.2017.1335274 [doi]
AB  - The Rho GTPase family members Rac1, Cdc42 and RhoA play key contributory roles in 
      the transformed phenotype of human cancers. Epithelial Cell Transforming Sequence 
      2 (Ect2), a guanine nucleotide exchange factor (GEF) for these Rho GTPases, has 
      also been implicated in a variety of human cancers. We have shown that Ect2 is 
      frequently overexpressed in both major forms of non-small cell lung cancer 
      (NSCLC), lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC), 
      which together make up approximately 70% of all lung cancer diagnoses. 
      Furthermore, we have found that Ect2 is required for multiple aspects of the 
      transformed phenotype of NSCLC cells including transformed growth and invasion in 
      vitro and tumorigenesis in vivo. More recently, we showed that a major mechanism 
      by which Ect2 drives KRAS-mediated LADC transformation is by regulating rRNA 
      (rRNA) synthesis. However, it remains unclear whether Ect2 plays a similar role 
      in ribosome biogenesis in LSCC. Here we demonstrate that Ect2 expression 
      correlates positively with expression of ribosome biogenesis genes and with 
      pre-ribosomal 45S RNA abundance in primary LSCC tumors. Furthermore, we 
      demonstrate that Ect2 functionally regulates rRNA synthesis in LSCC cells. Based 
      on these data, we propose that inhibition of Ect2-mediated nucleolar signaling 
      holds promise as a potential therapeutic strategy for improved treatment of both 
      LADC and LSCC.
FAU - Justilien, Verline
AU  - Justilien V
AD  - a Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center , 
      Jacksonville , FL , USA.
FAU - Lewis, Kayla C
AU  - Lewis KC
AD  - a Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center , 
      Jacksonville , FL , USA.
FAU - Murray, Nicole R
AU  - Murray NR
AD  - a Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center , 
      Jacksonville , FL , USA.
FAU - Fields, Alan P
AU  - Fields AP
AD  - a Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center , 
      Jacksonville , FL , USA.
LA  - eng
GR  - R21 CA204938/CA/NCI NIH HHS/United States
GR  - R01 CA081436/CA/NCI NIH HHS/United States
GR  - R21 CA180997/CA/NCI NIH HHS/United States
GR  - R21 CA151250/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Video-Audio Media
DEP - 20170705
PL  - United States
TA  - Small GTPases
JT  - Small GTPases
JID - 101530974
RN  - 0 (ECT2 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (RNA, Ribosomal)
SB  - IM
MH  - Animals
MH  - Carcinogenesis/*metabolism/pathology
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism/pathology
MH  - Humans
MH  - Lung Neoplasms/*metabolism/pathology
MH  - Neoplasm Invasiveness
MH  - Proto-Oncogene Proteins/*metabolism
MH  - RNA, Neoplasm/*biosynthesis
MH  - RNA, Ribosomal/*biosynthesis
MH  - Ribosomes/metabolism/pathology
MH  - *Signal Transduction
PMC - PMC6748369
OTO - NOTNLM
OT  - Ect2
OT  - non-small cell lung cancer
OT  - rRNA synthesis
OT  - ribosome biogenesis
EDAT- 2017/06/29 06:00
MHDA- 2020/04/10 06:00
PMCR- 2018/07/05
CRDT- 2017/06/29 06:00
PHST- 2017/06/29 06:00 [pubmed]
PHST- 2020/04/10 06:00 [medline]
PHST- 2017/06/29 06:00 [entrez]
PHST- 2018/07/05 00:00 [pmc-release]
AID - 1335274 [pii]
AID - 10.1080/21541248.2017.1335274 [doi]
PST - ppublish
SO  - Small GTPases. 2019 Sep;10(5):388-394. doi: 10.1080/21541248.2017.1335274. Epub 
      2017 Jul 5.