TY - JOUR
T1 - PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes
AU - Singh, Deepak K.
AU - Gholamalamdari, Omid
AU - Jadaliha, Mahdieh
AU - Li, Xiao Ling
AU - Lin, Yo Chuen
AU - Zhang, Yang
AU - Guang, Shuomeng
AU - Hashemikhabir, Seyedsasan
AU - Tiwari, Saumya
AU - Zhu, Yuelin J.
AU - Khan, Abid
AU - Thomas, Anu
AU - Chakraborty, Arindam
AU - Macias, Virgilia
AU - Balla, Andre K.
AU - Bhargava, Rohit
AU - Janga, Sarath Chandra
AU - Ma, Jian
AU - Prasanth, Supriya G.
AU - Lal, Ashish
AU - Prasanth, Kannanganattu V.
N1 - Funding Information:
This work was supported by grants from National Institute of Health (1RO1GM088252 to K.V.P., 1RO1GM099669 to S.G.P.); American Cancer Society (RSG-11-174-01-RMC to K.V.P.); National Science Foundation (1723008 to K.V.P., 1243372 to S.G.P). We would like to thank Drs. Ray P. (Carle Foundation Hospital) and members of Prasanth KV and SG laboratories for their valuable suggestions. Conflict of Interest Statement: None declared.
Publisher Copyright:
© The Author 2017. Published by Oxford University Press. All rights reserved.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatinassociated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.
AB - Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatinassociated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.
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U2 - 10.1093/carcin/bgx062
DO - 10.1093/carcin/bgx062
M3 - Article
C2 - 28633434
AN - SCOPUS:85032439489
SN - 0143-3334
VL - 38
SP - 966
EP - 975
JO - Carcinogenesis
JF - Carcinogenesis
IS - 10
M1 - bgx062
ER -
