PMID- 27872141
OWN - NLM
STAT- MEDLINE
DCOM- 20180213
LR  - 20181202
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Linking)
VI  - 24
IP  - 1
DP  - 2017 Jan
TI  - Differential roles of RET isoforms in medullary and papillary thyroid carcinomas.
PG  - 53-69
AB  - The RET receptor tyrosine kinase mediates cell proliferation, survival and 
      migration in embryogenesis and is implicated in the transformation and tumour 
      progression in multiple cancers. RET is frequently mutated and constitutively 
      activated in familial and sporadic thyroid carcinomas. As a result of alternative 
      splicing, RET is expressed as two protein isoforms, RET9 and RET51, which differ 
      in their unique C-terminal amino acids. These isoforms have distinct 
      intracellular trafficking and associated signalling complexes, but functional 
      differences are not well defined. We used shRNA-mediated knockdown (KD) of 
      individual RET isoforms or of total RET to evaluate their functional 
      contributions in thyroid carcinoma cells. We showed that RET is required for cell 
      survival in medullary (MTC) but not papillary thyroid carcinoma (PTC) cells. In 
      PTC cells, RET depletion reduced cell migration and induced a flattened 
      epithelial-like morphology. RET KD decreased the expression of mesenchymal 
      markers and matrix metalloproteinases and reduced anoikis resistance and invasive 
      potential. Further, we showed that RET51 depletion had significantly greater 
      effects on each of these processes than RET9 depletion in both MTC and PTC cells. 
      Finally, we showed that expression of RET, particularly RET51, was correlated 
      with malignancy in a panel of human thyroid tumour tissues. Together, our data 
      show that RET expression promotes a more mesenchymal phenotype with reduced 
      cell-cell adhesion and increased invasiveness in PTC cell models, but is more 
      important for tumour cell survival, proliferation and anoikis resistance in MTC 
      models. Our data suggest that the RET51 isoform plays a more prominent role in 
      mediating these processes compared to RET9.
CI  - (c) 2017 Society for Endocrinology.
FAU - Lian, Eric Y
AU  - Lian EY
AD  - Division of Cancer Biology and GeneticsCancer Research Institute, Queen's 
      University, Kingston, Ontario, Canada.
AD  - Department of Pathology & Molecular MedicineQueen's University, Kingston, 
      Ontario, Canada.
FAU - Maritan, Sarah M
AU  - Maritan SM
AD  - Division of Cancer Biology and GeneticsCancer Research Institute, Queen's 
      University, Kingston, Ontario, Canada.
AD  - Department of Pathology & Molecular MedicineQueen's University, Kingston, 
      Ontario, Canada.
FAU - Cockburn, Jessica G
AU  - Cockburn JG
AD  - Division of Cancer Biology and GeneticsCancer Research Institute, Queen's 
      University, Kingston, Ontario, Canada.
AD  - Department of Pathology & Molecular MedicineQueen's University, Kingston, 
      Ontario, Canada.
FAU - Kasaian, Katayoon
AU  - Kasaian K
AD  - Michael Smith Genome Sciences CentreBritish Columbia Cancer Research Centre, 
      Vancouver, British Columbia, Canada.
FAU - Crupi, Mathieu J F
AU  - Crupi MJ
AD  - Division of Cancer Biology and GeneticsCancer Research Institute, Queen's 
      University, Kingston, Ontario, Canada.
AD  - Department of Pathology & Molecular MedicineQueen's University, Kingston, 
      Ontario, Canada.
FAU - Hurlbut, David
AU  - Hurlbut D
AD  - Department of Pathology & Molecular MedicineQueen's University, Kingston, 
      Ontario, Canada.
FAU - Jones, Steven J M
AU  - Jones SJ
AD  - Michael Smith Genome Sciences CentreBritish Columbia Cancer Research Centre, 
      Vancouver, British Columbia, Canada.
AD  - Department of Medical GeneticsUniversity of British Columbia, British Columbia 
      Cancer Research Centre, Vancouver, British Columbia, Canada.
FAU - Wiseman, Sam M
AU  - Wiseman SM
AD  - Department of SurgerySt Paul's Hospital & University of British Columbia, 
      Vancouver, British Columbia, Canada.
FAU - Mulligan, Lois M
AU  - Mulligan LM
AD  - Division of Cancer Biology and GeneticsCancer Research Institute, Queen's 
      University, Kingston, Ontario, Canada mulligal@queensu.ca.
AD  - Department of Pathology & Molecular MedicineQueen's University, Kingston, 
      Ontario, Canada.
LA  - eng
GR  - MOP-142303/CIHR/Canada
PT  - Journal Article
DEP - 20161121
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
RN  - Thyroid cancer, medullary
SB  - IM
MH  - Carcinoma, Neuroendocrine/genetics/*metabolism
MH  - Carcinoma, Papillary/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Female
MH  - Humans
MH  - Lymphatic Metastasis/genetics
MH  - Male
MH  - Middle Aged
MH  - Protein Isoforms/genetics/metabolism
MH  - Proto-Oncogene Proteins c-ret/genetics/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Thyroid Cancer, Papillary
MH  - Thyroid Gland/metabolism
MH  - Thyroid Neoplasms/genetics/*metabolism
OTO - NOTNLM
OT  - RET isoforms
OT  - epithelial-mesenchymal transition
OT  - invasion
OT  - migration
OT  - thyroid carcinoma
EDAT- 2016/11/23 06:00
MHDA- 2018/02/14 06:00
CRDT- 2016/11/23 06:00
PHST- 2016/11/18 00:00 [received]
PHST- 2016/11/21 00:00 [accepted]
PHST- 2016/11/23 06:00 [pubmed]
PHST- 2018/02/14 06:00 [medline]
PHST- 2016/11/23 06:00 [entrez]
AID - ERC-16-0393 [pii]
AID - 10.1530/ERC-16-0393 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2017 Jan;24(1):53-69. doi: 10.1530/ERC-16-0393. Epub 2016 
      Nov 21.