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KRCC1: A potential therapeutic target in ovarian cancer
Author(s) -
Dwivedi Shailendra Kumar Dhar,
Shameer Khader,
Dey Anindya,
Mustafi Soumyajit Banerjee,
Xiong Xunhao,
Bhattacharya Udayan,
NeizerAshun Fiifi,
Rao Geeta,
Wang Yue,
Ivan Cristina,
Yang Da,
Dudley Joel T.,
Xu Chao,
Wren Jonathan D.,
Mukherjee Priyabrata,
Bhattacharya Resham
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902259r
Subject(s) - ovarian cancer , medicine , oncology , cancer research , cancer
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.