Andre K. Balla, Ashish Lal, Anu Thomas, Yuelin J. Zhu, Supriya G. Prasanth, Arindam Chakraborty, Xiao Ling Li, Kannanganattu V. Prasanth, Shuomeng Guang, Jian Ma, Virgilia Macias, Omid Gholamalamdari, Deepak K. Singh, Saumya Tiwari, Seyedsasan Hashemikhabir, Mahdieh Jadaliha, Rohit Bhargava, Yang Zhang, Yo-Chuen Lin, Abid Khan, Sarath Chandra Janga
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in breast cancer initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in breast cancer 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.