PMID- 28664913
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 117
IP  - 4
DP  - 2017 Jun 29
TI  - KIBRA attains oncogenic activity by repressing RASSF1A.
PG  - 553-62
LID - 10.1038/bjc.2017.192 [doi]
AB  - BACKGROUND: KIBRA-initially identified as a neuronal associated protein is now 
      shown to be functionally associated with other tissue types as well. KIBRA 
      interacts with dyenin light chain 1 and this interaction is essential for 
      oestrogen receptor transactivation in breast cancer cells. KIBRA as a substrate 
      of Cdk1, Aurora kinase and ERK plays an important role in regulating cell cycle, 
      cell proliferation and migration. Despite these evidences, the exact role of 
      KIBRA in cancer progression is not known. METHODS: We studied the expression of 
      KIBRA in breast tissues and breast cancer cell lines by western blotting, 
      immunohistochemisry (IHC) and RT-PCR. Stable over expression and knockdown clones 
      were generated to study the transforming properties of KIBRA by conventional 
      assays. Xenograft studies were performed in nude mice to study the in vivo 
      tumourigenic efficacy of KIBRA. qPCR array was performed to understand the 
      molecular mechanism behind oncogenic activity of KIBRA. RESULTS: Our results 
      showed that KIBRA is upregulated in breast cancer cells and in malignant human 
      breast tumours by both western blotting and IHC. Interestingly, we found that 
      KIBRA expression level goes up with increase in breast cancer progression in 
      well-established MCF10A model system. Further, results from stable overexpression 
      clones of KIBRA in fibroblasts (Rat-1) and epithelial breast cancer cells (ZR75) 
      and lentiviral short hairpin RNA-mediated knockdown (KD) clones of KIBRA in ZR75 
      showed increase in transforming properties with KIBRA overexpression and 
      vice-versa. Results also showed that fibroblasts stably overexpressing KIBRA 
      showed increased tumourigenic potential in nude mice. By adopting a quantitative 
      PCR array-based approach, we identified RASSF1A, a tumour suppressor, as a 
      transcriptional target of KIBRA. CONCLUSIONS: This is the first study to 
      demonstrate the in vivo tumourigenic property of KIBRA in a nude mouse model and 
      also unravel the underlying molecular mechanism of KIBRA-mediated transformation 
      via repression of RASSF1A.British Journal of Cancer advance online publication, 
      29 June 2017; doi:10.1038/bjc.2017.192 www.bjcancer.com.
FAU - Anuj
AU  - Anuj
AD  - Department of Biotechnology, Indian Institute of Technology Madras (IITM), 
      Chennai 600036, India.
FAU - Arivazhagan, Lakshmi
AU  - Arivazhagan L
AD  - Department of Biotechnology, Indian Institute of Technology Madras (IITM), 
      Chennai 600036, India.
FAU - Surabhi, Rohan Prasad
AU  - Surabhi RP
AD  - Department of Biotechnology, Indian Institute of Technology Madras (IITM), 
      Chennai 600036, India.
FAU - Kanakarajan, Archana
AU  - Kanakarajan A
AD  - Pathology, Sri Ramachandra University, Porur, Chennai 600116, India.
FAU - Sundaram, Sandhya
AU  - Sundaram S
AD  - Pathology, Sri Ramachandra University, Porur, Chennai 600116, India.
FAU - Pitani, Ravi Shankar
AU  - Pitani RS
AD  - Community Medicine, Sri Ramachandra University, Porur, Chennai 600116, India.
FAU - Mudduwa, Lakmini
AU  - Mudduwa L
AD  - Department of Pathology, Faculty of Medicine, University of Ruhuna, Galle 80000, 
      Sri Lanka.
FAU - Kremerskothen, Joachim
AU  - Kremerskothen J
AD  - Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, 
      University Hospital Muenster, Muenster 48149, Germany.
FAU - Venkatraman, Ganesh
AU  - Venkatraman G
AD  - Departments of Human Genetics, Sri Ramachandra University, Porur, Chennai 600116, 
      India.
FAU - Rayala, Suresh K
AU  - Rayala SK
AD  - Department of Biotechnology, Indian Institute of Technology Madras (IITM), 
      Chennai 600036, India.
LA  - eng
PT  - Journal Article
DEP - 20170629
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
PMC - PMC5558681
COIS- The authors declare no conflict of interest.
EDAT- 2017/07/01 06:00
MHDA- 2017/07/01 06:00
PMCR- 2018/08/08
CRDT- 2017/07/01 06:00
PHST- 2017/01/22 00:00 [received]
PHST- 2017/05/24 00:00 [revised]
PHST- 2017/05/30 00:00 [accepted]
PHST- 2017/07/01 06:00 [entrez]
PHST- 2017/07/01 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2018/08/08 00:00 [pmc-release]
AID - bjc2017192 [pii]
AID - 10.1038/bjc.2017.192 [doi]
PST - aheadofprint
SO  - Br J Cancer. 2017 Jun 29;117(4):553-62. doi: 10.1038/bjc.2017.192.