Kinesin-like protein KIFC1, a normally nonessential kinesin motor, plays critical role in centrosome clustering cancer cells and is essential for the survival of cells. Herein, we reported that KIFC1 expression up-regulated breast cancer, particularly estrogen receptor negative, progesterone negative triple not associated with epidermal growth factor 2 status. In addition, highly expressed all 8 tested human cell lines, but absent normal mammary epithelial weakly lung fibroblast lines....

The Fc receptor-like protein 5 (FCRL5) on B cells has both an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence and two consensus inhibitory motifs (ITIM) in its cytoplasmic region. To evaluate signaling potential, we expressed constructs for chimeric molecules composed of the region FCRL5 extracellular transmembrane regions IgG receptor FcγRIIB a cell line lacking endogenous receptor. Coligation this fusion with (BCR) inhibited BCR-mediated calcium mobilization,...

Historically, drugs used in the treatment of cancers also tend to cause damage healthy cells while affecting cancer cells. Therefore, identification novel agents that act specifically against remains a high priority search for new therapies. In contrast with normal cells, most contain multiple centrosomes which are associated genome instability and tumorigenesis. Cancer can avoid multipolar mitosis, cell death, by clustering extra into two spindle poles, thereby enabling bipolar division....

Defects in the apoptotic machinery can contribute to tumor formation and resistance treatment, creating a need identify new agents that kill cancer cells by alternative mechanisms. To this end, we examined cytotoxic properties of novel peptide, CT20p, derived from C-terminal, alpha-9 helix Bax, an amphipathic domain with putative membrane binding properties. Like many antimicrobial peptides, CT20p contains clusters hydrophobic cationic residues could enable peptide associate lipid membranes....

Metastasis accounts for most deaths from breast cancer, driving the need new therapeutics that can impede disease progression. Rationally designed peptides take advantage of cancer-specific differences in cellular physiology are an emerging technology offer promise as a treatment metastatic cancer. We developed CT20p, hydrophobic peptide based on C terminus Bax exhibits similarities with antimicrobial peptides, and previously reported CT20p has unique cytotoxic actions independent...

The dual functionality of the tumor suppressor BAX is implied by nonapoptotic functions other members BCL-2 family. To explore this, mitochondrial metabolism was examined in BAX-deficient HCT-116 cells as well primary hepatocytes from mice. Although density and DNA content were same BAX-containing cells, MitoTracker staining patterns differed, suggesting existence BAX-dependent functional differences physiology. Oxygen consumption cellular ATP levels reduced while glycolysis increased. These...

// Ning Liu 1, 2, * , Rebecca J. Boohaker Chunling Jiang 3, 4, James R. 5 Bo Xu 6 1 Department of Oncology, Southern Research Institute, Birmingham, AL 35205, USA 2 Gastric Cancer Surgery, Tianjin Medical University Institute and Hospital, National Clinical Center for Cancer, Key Laboratory Prevention Therapy, 300060, China 3 Nanchang Graduate School, 330047, 4 Radiation Jiangxi 330029, Economics, American University, Washington, DC 20016, Cell Biology Program, Comprehensive Center, Alabama...

Anaplastic thyroid cancer (ATC) is an aggressive with poor clinical prognosis. However, mechanisms driving ATC aggressiveness not well known. Components of the DNA damage response (DDR) are frequently found mutated or aberrantly expressed in ATC. The goal this study to establish functional link between histone acetyltransferase lysine (K) 5 (KAT5, a critical DDR protein) and invasiveness using clinical, vitro vivo models. We analyzed expression KAT5 by immunohistochemistry assessed its...

Pancreatic cancer is a highly lethal disease with obesity as one of the risk factors. Oncogenic KRAS mutations are prevalent in pancreatic and can rewire lipid metabolism by altering fatty acid (FA) uptake, FA oxidation (FAO), lipogenesis. Identification underlying mechanisms could lead to improved therapeutic strategies for treating KRAS-mutant cancer. Here, we observed that KRASG12D upregulated expression SLC25A1, citrate transporter key metabolic switch mediate FAO, synthesis, glycolysis,...

Apoptosis is a complex process essential for normal tissue development and cellular homeostasis. While biochemical events that occur late in the apoptotic are better characterized, early physiological changes initiate progression of cell death remain poorly understood. Previously, we observed lymphocytes, undergoing apoptosis response to growth factor withdrawal, experienced rapid transient rise cytosolic pH. We found protein responsible was pH-regulating, plasma membrane Na(+)/H(+)...

There is an unmet clinical need to identify biomarkers for breast cancer neoadjuvant chemotherapy. Here, using miRNA TaqMan Low-Density Arrays (TLDA), we analyzed the expression profile in pre-treatment needle aspiration tumor samples from patients who received taxane-anthracycline-based Although, unsupervised hierarchical cluster analysis, total could not generate a tree with clear distinction between pathologic complete response (pCR) and non-pCR classes, found that elevated of miR-125b...

// Timothy P. Wakeman 1, 2, * , Aimin Yang 3, Naresh S. Dalal 4 Rebecca J. Boohaker 5 Qinghua Zeng Qiang Ding 6 and Bo Xu 1 Department of Biochemistry Molecular Biology, LSU Health Sciences Center, New Orleans, LA, USA 2 Genetics, 3 Nuclear Medicine, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China Chemistry Biochemistry, Florida State Tallahassee, FL, Oncology, The Southern Research Institute, Birmingham, AL, Cell, Developmental, Integrative University Alabama at These...

Abstract The alpha-fetoprotein receptor (AFPR) is a novel target for cancer therapeutics. It expressed on most cancers and myeloid derived suppressor cells (MDSCs) but generally absent normal tissues. Studies were performed to investigate the use of recombinant human AFP (ACT-101) conjugated with maytansinoid toxins targeted toxin delivery cancer. Four structurally different ACT-101-maytansinoid conjugates containing cleavable glutathione sensitive linkers initially investigated in mouse...

Both the DNA damage response (DDR) and mitotic checkpoint are critical for maintenance of genomic stability. Among proteins involved in these processes, ataxia-telangiectasia mutated (ATM) kinase is required both activation DDR spindle assembly (SAC). In mitosis without damage, enzymatic activity ATM enhanced; however, substrates unknown. Using stable isotope labeling amino acids cell culture mass spectrometry analysis, we identified a number that can potentially be phosphorylated by during...

Resistance to radiation and chemotherapy in colorectal cancer (CRC) patients contribute significantly refractory disease progression. Herein, we provide mechanistic rationale for acquired or inherent chemotherapeutic resistance the anti-tumor effects of 5-fluorouracil (5-FU) that is linked oncogenic GLI1 transcription activity NBS1 overexpression. Patients with high levels also expressed NBS1. Non-canonical activation driven through pathways CRC, like BRAFV600E mutation. was identified as a...

Mitotic kinesin Eg5 is an attractive anticancer drug target. Discovery of inhibitors has been focused on targeting the 'monastrol-binding site'. However, acquired resistance reported for such inhibitors. Therefore, identifying new which function through a different mechanism(s) could complement current candidates and improve efficacy. In this study, we explored novel allosteric site identified structure-based virtual screening. Experiments with saturation-transfer difference NMR demonstrated...

ABSTRACT Host genotype influences the severity of murine Lyme borreliosis, caused by spirochetal bacterium Borrelia burgdorferi . C57BL/6 (B6) mice develop mild arthritis, whereas C3H/HeN (C3H) severe arthritis. Differential expression interleukin 10 (IL-10) has long been associated with mouse strain differences in pathogenesis; however, underlying mechanism(s) this genotype-specific IL-10 regulation remained elusive. Herein we reveal a cAMP-mediated mechanism B6 macrophages that is...

Abstract Tumor cells exploit immune checkpoints by expressing checkpoint ligands such as PD-L1, effectively masking them from destruction. Programmed cell death- 1 (PD-1), plays a major role in tumor escape. The interaction of PD-1/PD-L1 inhibits cytotoxic T lymphocyte (CTL) proliferation, induces apoptosis tumor-specific cells, and promotes the resistance to CTL attack. Monoclonal antibodies these proteins have been developed approved for use clinic. Theoretically, peptide mimics, which...

Chaperonin containing TCP1 (CCT/TRiC) is a multi-subunit protein folding complex that enables the cancer phenotype to emerge from mutational landscape drives oncogenesis. We and others linked increased expression of CCT subunits advanced tumor stage invasiveness inversely correlates with patient outcomes. In this study, we examined second subunit, CCT2, using genomic databases adult pediatric tumors normal tissues, found it was highly expressed in cancers, showing significant difference...

Epigenetic dysregulation characterized by aberrant DNA hypermethylation is a hallmark of cancer, and it can be targeted hypomethylating agents (HMAs). Recently, we described the superior therapeutic efficacy novel HMA, namely, NTX-301, when used as monotherapy in combination with venetoclax treatment acute myeloid leukemia. Following previous study, further explored properties NTX-301 based on experimental investigations integrative data analyses. Comprehensive sensitivity profiling revealed...