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Ror2, a Developmentally Regulated Kinase, Is Associated With Tumor Growth, Apoptosis, Migration, and Invasion in Renal Cell Carcinoma.

Abstract Renal cell carcinoma (RCC) represents one of the most resistant tumors to radiation and chemotherapy. Current therapies for RCC patients are inefficient due to the lack of diagnostic and therapeutic markers. The expression of novel tumor-associated kinases has the potential to dramatically shape tumor cell behavior. Identifying tumor-associated kinases can lend insight into patterns of tumor growth and characteristics. In the present study, we investigated the receptor tyrosine kinase-like orphan receptor 2 (Ror2), a new tumor-associated kinase, in RCC primary tumors and cell lines. Knockdown of Ror2 expression in RCC cells with specific shRNA significantly reduced cell proliferation and induced apoptosis. Using in vitro migration and Matrigel invasion assays, we found that cell migration and invasive ability were also significantly inhibited. In RCC, Ror2 expression correlated with expression of genes involved at the cell cycle and migration, including PCNA, CDK1, TWIST, and MMP-2. Furthermore, in vivo xenograft studies in nude mice revealed that administration of a Ror2 shRNA plasmid significantly inhibited tumor growth. These findings suggest a novel pathway of tumor-promoting activity by Ror2 within renal carcinomas, with significant implications for unraveling the tumorigenesis of RCC.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title oncology research
Publication Year Start




PMID- 28277191
OWN - NLM
STAT- MEDLINE
DA  - 20170309
DCOM- 20170316
LR  - 20170316
IS  - 1555-3906 (Electronic)
IS  - 0965-0407 (Linking)
VI  - 25
IP  - 2
DP  - 2017 Jan 26
TI  - Ror2, a Developmentally Regulated Kinase, Is Associated With Tumor Growth,
      Apoptosis, Migration, and Invasion in Renal Cell Carcinoma.
PG  - 195-205
LID - 10.3727/096504016X14732772150424 [doi]
AB  - Renal cell carcinoma (RCC) represents one of the most resistant tumors to
      radiation and chemotherapy. Current therapies for RCC patients are inefficient
      due to the lack of diagnostic and therapeutic markers. The expression of novel
      tumor-associated kinases has the potential to dramatically shape tumor cell
      behavior. Identifying tumor-associated kinases can lend insight into patterns of 
      tumor growth and characteristics. In the present study, we investigated the
      receptor tyrosine kinase-like orphan receptor 2 (Ror2), a new tumor-associated
      kinase, in RCC primary tumors and cell lines. Knockdown of Ror2 expression in RCC
      cells with specific shRNA significantly reduced cell proliferation and induced
      apoptosis. Using in vitro migration and Matrigel invasion assays, we found that
      cell migration and invasive ability were also significantly inhibited. In RCC,
      Ror2 expression correlated with expression of genes involved at the cell cycle
      and migration, including PCNA, CDK1, TWIST, and MMP-2. Furthermore, in vivo
      xenograft studies in nude mice revealed that administration of a Ror2 shRNA
      plasmid significantly inhibited tumor growth. These findings suggest a novel
      pathway of tumor-promoting activity by Ror2 within renal carcinomas, with
      significant implications for unraveling the tumorigenesis of RCC.
FAU - Yang, Chun-Ming
AU  - Yang CM
AD  - Department of Urology, The First Affiliated Hospital, China Medical University,
      Shenyang, P.R. China.
FAU - Ji, Shan
AU  - Ji S
FAU - Li, Yan
AU  - Li Y
FAU - Fu, Li-Ye
AU  - Fu LY
FAU - Jiang, Tao
AU  - Jiang T
FAU - Meng, Fan-Dong
AU  - Meng FD
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncol Res
JT  - Oncology research
JID - 9208097
RN  - EC 2.7.10.1 (ROR2 protein, human)
RN  - EC 2.7.10.1 (Receptor Tyrosine Kinase-like Orphan Receptors)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Carcinogenesis/*metabolism
MH  - Carcinoma, Renal Cell/*enzymology/genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/*physiology
MH  - Humans
MH  - Kidney Neoplasms/*enzymology/genetics
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Invasiveness/genetics/pathology
MH  - Receptor Tyrosine Kinase-like Orphan Receptors/*biosynthesis/genetics
MH  - Xenograft Model Antitumor Assays/methods
EDAT- 2017/03/10 06:00
MHDA- 2017/03/17 06:00
CRDT- 2017/03/10 06:00
AID - 10.3727/096504016X14732772150424 [doi]
PST - ppublish
SO  - Oncol Res. 2017 Jan 26;25(2):195-205. doi: 10.3727/096504016X14732772150424.

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