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 Gangadharan Prasanth, Ashish LalPrasanth Kumar Kannanganattu

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

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Triple Negative Breast Neoplasms
cdc Genes
Breast Neoplasms
RNA Polymerase II
Cell Line
Ductal Carcinoma
Proteins
Survival Analysis
Cell Cycle Checkpoints
Chromatin
Cell Movement
Immunohistochemistry
Neoplasm Metastasis
Gene Expression
Survival
Neoplasms

ASJC Scopus subject areas

  • Cancer Research

Cite this

PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes. / Singh, Deepak K.; Gholamalamdari, Omid; Jadaliha, Mahdieh; Li, Xiao Ling; Lin, Yo Chuen; Zhang, Yang; Guang, Shuomeng; Hashemikhabir, Seyedsasan; Tiwari, Saumya; Zhu, Yuelin J.; Khan, Abid; Thomas, Anu; Chakraborty, Arindam; Macias, Virgilia; Balla, Andre K.; Bhargava, Rohit; Janga, Sarath Chandra; Ma, Jian; Prasanth, Supriya Gangadharan; Lal, Ashish; Kannanganattu, Prasanth Kumar.

In: Carcinogenesis, Vol. 38, No. 10, bgx062, 01.10.2017, p. 966-975.

Research output: Contribution to journalArticle

Singh, DK, Gholamalamdari, O, Jadaliha, M, Li, XL, Lin, YC, Zhang, Y, Guang, S, Hashemikhabir, S, Tiwari, S, Zhu, YJ, Khan, A, Thomas, A, Chakraborty, A, Macias, V, Balla, AK, Bhargava, R, Janga, SC, Ma, J, Prasanth, SG, Lal, A & Kannanganattu, PK 2017, 'PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes', Carcinogenesis, vol. 38, no. 10, bgx062, pp. 966-975. https://doi.org/10.1093/carcin/bgx062
Singh DK, Gholamalamdari O, Jadaliha M, Li XL, Lin YC, Zhang Y et al. PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes. Carcinogenesis. 2017 Oct 1;38(10):966-975. bgx062. https://doi.org/10.1093/carcin/bgx062
Singh, Deepak K. ; Gholamalamdari, Omid ; Jadaliha, Mahdieh ; Li, Xiao Ling ; Lin, Yo Chuen ; Zhang, Yang ; Guang, Shuomeng ; Hashemikhabir, Seyedsasan ; Tiwari, Saumya ; Zhu, Yuelin J. ; Khan, Abid ; Thomas, Anu ; Chakraborty, Arindam ; Macias, Virgilia ; Balla, Andre K. ; Bhargava, Rohit ; Janga, Sarath Chandra ; Ma, Jian ; Prasanth, Supriya Gangadharan ; Lal, Ashish ; Kannanganattu, Prasanth Kumar. / PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes. In: Carcinogenesis. 2017 ; Vol. 38, No. 10. pp. 966-975.
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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 Gangadharan

AU - Lal, Ashish

AU - Kannanganattu, Prasanth Kumar

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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