TY - JOUR
T1 - KRCC1
T2 - A potential therapeutic target in ovarian cancer
AU - Dwivedi, Shailendra Kumar Dhar
AU - Shameer, Khader
AU - Dey, Anindya
AU - Mustafi, Soumyajit Banerjee
AU - Xiong, Xunhao
AU - Bhattacharya, Udayan
AU - Neizer-Ashun, Fiifi
AU - Rao, Geeta
AU - Wang, Yue
AU - Ivan, Cristina
AU - Yang, Da
AU - Dudley, Joel T.
AU - Xu, Chao
AU - Wren, Jonathan D.
AU - Mukherjee, Priyabrata
AU - Bhattacharya, Resham
N1 - Publisher Copyright:
© 2019 Federation of American Societies for Experimental Biology
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Using a systems biology approach to prioritize potential points of intervention in ovarian cancer, we identified the lysine rich coiled-coil 1 (KRCC1), as a potential target. High-grade serous ovarian cancer patient tumors and cells express significantly higher levels of KRCC1 which correlates with poor overall survival and chemoresistance. We demonstrate that KRCC1 is predominantly present in the chromatin-bound nuclear fraction, interacts with HDAC1, HDAC2, and with the serine-threonine phosphatase PP1CC. Silencing KRCC1 inhibits cellular plasticity, invasive properties, and potentiates apoptosis resulting in reduced tumor growth. These phenotypes are associated with increased acetylation of histones and with increased phosphorylation of H2AX and CHK1, suggesting the modulation of transcription and DNA damage that may be mediated by the action of HDAC and PP1CC, respectively. Hence, we address an urgent need to develop new targets in cancer.
AB - Using a systems biology approach to prioritize potential points of intervention in ovarian cancer, we identified the lysine rich coiled-coil 1 (KRCC1), as a potential target. High-grade serous ovarian cancer patient tumors and cells express significantly higher levels of KRCC1 which correlates with poor overall survival and chemoresistance. We demonstrate that KRCC1 is predominantly present in the chromatin-bound nuclear fraction, interacts with HDAC1, HDAC2, and with the serine-threonine phosphatase PP1CC. Silencing KRCC1 inhibits cellular plasticity, invasive properties, and potentiates apoptosis resulting in reduced tumor growth. These phenotypes are associated with increased acetylation of histones and with increased phosphorylation of H2AX and CHK1, suggesting the modulation of transcription and DNA damage that may be mediated by the action of HDAC and PP1CC, respectively. Hence, we address an urgent need to develop new targets in cancer.
KW - KRCC1
KW - ovarian cancer
KW - systems biology
UR - http://www.scopus.com/inward/record.url?scp=85078674542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078674542&partnerID=8YFLogxK
U2 - 10.1096/fj.201902259R
DO - 10.1096/fj.201902259R
M3 - Article
C2 - 31908025
AN - SCOPUS:85078674542
SN - 0892-6638
VL - 34
SP - 2287
EP - 2300
JO - FASEB Journal
JF - FASEB Journal
IS - 2
ER -