Enhanced expression of histone chaperone APLF associate with breast cancer.

Abstract

DNA damage-specific histone chaperone Aprataxin PNK-like factor (APLF) regulates mesenchymal-to-epithelial transition (MET) during cellular reprogramming. We investigated the role of APLF in epithelial-to-mesenchymal transition (EMT) linked to breast cancer invasiveness and metastasis. Here, we show that a significant manifestation of APLF is present in tumor sections of patients with invasive ductal carcinoma when compared to their normal adjacent tissues. APLF was significantly induced in triple negative breast cancer (TNBC) cells, MDAMB-231, in comparison to invasive MCF7 or normal MCF10A breast cells and supported by studies on invasive breast carcinoma in The Cancer Genome Atlas (TCGA). Functionally, APLF downregulation inhibited proliferative capacity, altered cell cycle behavior, induced apoptosis and impaired DNA repair ability of MDAMB-231 cells. Reduction in APLF level impeded invasive, migratory, tumorigenic and metastatic potential of TNBC cells with loss in expression of genes associated with EMT while upregulation of MET-specific gene E-cadherin (CDH1). So, here we provided novel evidence for enrichment of APLF in breast tumors, which could regulate metastasis-associated EMT in invasive breast cancer. We anticipate that APLF could be exploited as a biomarker for breast tumors and additionally could be targeted in sensitizing cancer cells towards DNA damaging agents.

• Authors: Aditi Majumder, Khaja Moheiddin Syed, Ananda Mukherjee, Manendra Babu Lankadasari, Juberiya Mohammed Azeez, Sreeharshan Sreeja, Kuzhuvelil B Harikumar, Madhavan Radhakrishna Pillai, Debasree Dutta
• Journal: Molecular cancer (Mol Cancer) Vol. 17 Issue 1 Pg. 76 (03 26 2018) ISSN: 1476-4598 [Electronic] England
• PMID: 29580241 (Publication Type: Letter, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Poly-ADP-Ribose Binding Proteins
• APLF protein, human
• DNA-(Apurinic or Apyrimidinic Site) Lyase

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (metabolism, pathology)
• Carcinoma, Ductal, Breast (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• DNA-(Apurinic or Apyrimidinic Site) Lyase (metabolism)
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Neoplasm Transplantation
• Poly-ADP-Ribose Binding Proteins (metabolism)
• Tissue Array Analysis
• Triple Negative Breast Neoplasms (metabolism, pathology)
• Up-Regulation