Angiopoietin-like protein 4 is a chromatin-bound protein that enhances mammosphere formation in vitro and experimental triple-negative breast cancer brain and liver metastases in vivo

Abstract

INTRODUCTION: Metastatic progression in triple-negative breast cancer (TNBC) patients occurs primarily because of nuclear reprogramming that includes chromatin remodeling and epigenetic modifications. The existing and most successful chemotherapies available for metastatic TNBC target nuclear proteins or damage DNA. The objectives here are to investigate an undescribed role for the molecular biology of nuclear angiopoietin-like protein 4 (ANGPTL4) and to characterize the effect of ectopic overexpression of ANGPTL4 in the metastatic biology of TNBC. MATERIALS AND METHODS: Lentiviral-mediated transduction was used to overexpress ANGPTL4 in the TNBC cell line MD Anderson–metastatic breast cancer 231. The overexpression of ANGPTL4 was confirmed by western blot and ELISA. Subcellular fractionation, western blot, and immunofluorescence microscopy were used to characterize the intracellular localization of ANGPTL4. Mammosphere culture and the anchorage-independent growth assay analyzed the metastatic potential of the cell line. Xenograft assays assessed the effect of ANGPTL4 overexpression on TNBC metastases in vivo . RESULTS: The ANGPTL4 overexpressing cell line formed larger mammospheres and anchorage-independent colonies in vitro and developed larger primary tumors, more liver metastases, and brain metastatic outgrowth in vivo in comparison to a cell line that expressed endogenous levels of ANGPTL4. ANGPTL4, aurora kinase A (AURKA), a mitotic kinase, and Tat-interacting protein p60 kDa (Tip60), a lysine acetyltransferase, associated with chromatin in the ANGPTL4 overexpressing cells but not in cells that expressed endogenous levels of ANGPTL4. CONCLUSIONS: The ANGPTL4 overexpressing cell line showed in vitro and in vivo activities that suggest that nuclear ANGPTL4, AURKA, and Tip60 may cooperatively modulate TNBC metastases within chromatin-remodeling complexes or DNA-associated machinery.

Electrostatic potential difference between tumor and paratumor regulates cancer stem cell behavior and prognose tumor spread

“…Cryosections were prepared and stained for the CSC marker CD44 and examined under a fluorescent microscope (Figure 4). Other reported CSC markers were investigated, including GD2, 26 CD133, CD24, and ANGPTL4 27 . CD44 was chosen because of its prevalence in pan‐cancer CSCs.…”

“…Other reported CSC markers were investigated, including GD2, 26 CD133, CD24, and ANGPTL4. 27 CD44 was chosen because of its prevalence in pancancer CSCs. Dual-or triple staining was not adopted to avoid the high occurrence rate of false negatives.…”

Engineered Nanomaterials, Plants, Plant Toxicity and Biotransformation: A review

“…This study contributed to our understanding of the behavior of nanomaterials in plants. Determining the transformation of metal-based nanoparticles in plants, like other types of nanoparticles (such as polymer nanomaterials and carbon nanomaterials), is difficult because of the substantial background of the plant matrix and the shortage of effective approaches of spotting [112][113][114][115]. Although, there is no study which revealed the biotransformation of these nanomaterials in plants, this potential deformation should not be ignored [116][117][118][119][120][121][122].…”

Targeting autophagy with tamoxifen in breast cancer: From molecular mechanisms to targeted therapy

“…Breast cancer (BC) is one of the leading causes of mortality as well as the most prevalent type of cancer in women worldwide [1][2][3]. BC seems to be the cause of 18.2% of all cancer deaths, 16.2% of all female cancers, and 22.9% of invasive cancers [4].…”