PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes

Deepak K. Singh, Omid Gholamalamdari, Mahdieh Jadaliha, Xiao Ling Li, Yo Chuen Lin, Yang Zhang, Shuomeng Guang, Seyedsasan Hashemikhabir, Saumya Tiwari, Yuelin J. Zhu, Abid Khan, Anu Thomas, Arindam Chakraborty, Virgilia Macias, Andre K. Balla, Rohit Bhargava, Sarath Chandra Janga, Jian Ma, Supriya G. Prasanth, Ashish LalKannanganattu V. Prasanth

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numberbgx062
Pages (from-to)966-975
Number of pages10
JournalCarcinogenesis
Volume38
Issue number10
DOIs
StatePublished - Oct 1 2017

ASJC Scopus subject areas

  • Cancer Research

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    Singh, D. K., Gholamalamdari, O., Jadaliha, M., Li, X. L., Lin, Y. C., Zhang, Y., Guang, S., Hashemikhabir, S., Tiwari, S., Zhu, Y. J., Khan, A., Thomas, A., Chakraborty, A., Macias, V., Balla, A. K., Bhargava, R., Janga, S. C., Ma, J., Prasanth, S. G., ... Prasanth, K. V. (2017). PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes. Carcinogenesis, 38(10), 966-975. [bgx062]. https://doi.org/10.1093/carcin/bgx062