Infiltrating Myeloid Cells Exert Protumorigenic Actions via Neutrophil Elastase
This report suggests that MDSCs and NE are physiologically important mediators of prostate cancer progression and may serve as potential biomarkers and therapeutic targets. Mol Cancer Res; 15(9); 1138–52. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Lerman, I., Garcia-Hernandez, M. d. l. L., Rangel-Moreno, J., Chiriboga, L., Pan, C., Nastiuk, K. L., Krolewski, J. J., Sen, A., Hammes, S. R. Tags: Cell Death and Survival Source Type: research
Intratumor Heterogeneity: Novel Approaches for Resolving Genomic Architecture and Clonal Evolution
High-throughput genomic technologies have revealed a remarkably complex portrait of intratumor heterogeneity in cancer and have shown that tumors evolve through a reiterative process of genetic diversification and clonal selection. This discovery has challenged the classical paradigm of clonal dominance and brought attention to subclonal tumor cell populations that contribute to the cancer phenotype. Dynamic evolutionary models may explain how these populations grow within the ecosystem of tissues, including linear, branching, neutral, and punctuated patterns. Recent evidence in breast cancer favors branching and punctuate...
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Gupta, R. G., Somer, R. A. Tags: Review Source Type: research
Highlights of This Issue
(Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Tags: Highlights Source Type: research
eIF2{alpha} Phosphorylation Mediates IL24-Induced Apoptosis through Inhibition of Translation
IL24 is an immunomodulatory cytokine that also displays broad cancer-specific suppressor effects. The tumor-suppressor activities of IL24 include inhibition of angiogenesis, sensitization to chemotherapy, and cancer-specific apoptosis. Supra-physiologic activation and/or overexpression of translation initiation factors are implicated in the initiation and progression of cancer animal models as well as a subset of human cancers. Activation and/or overexpression of translation initiation factors correlate with aggressiveness of cancer and poor prognosis. Two rate-limiting translation initiation complexes, the ternary complex...
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Persaud, L., Zhong, X., Alvarado, G., Do, W., Dejoie, J., Zybtseva, A., Aktas, B. H., Sauane, M. Tags: Signal Transduction Source Type: research
Role of Rac1 Pathway in Epithelial-to-Mesenchymal Transition and Cancer Stem-like Cell Phenotypes in Gastric Adenocarcinoma
In conclusion, Rac1 promotes the EMT program in gastric adenocarcinoma and the acquisition of a CSC state. Rac1 inhibition in gastric adenocarcinoma cells blocks EMT and CSC phenotypes, and thus may prevent metastasis and augment chemotherapy.
Implications: In gastric adenocarcinoma, therapeutic targeting of the Rac1 pathway may prevent or reverse EMT and CSC phenotypes that drive tumor progression, metastasis, and chemotherapy resistance. Mol Cancer Res; 15(8); 1106–16. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Yoon, C., Cho, S.-J., Chang, K. K., Park, D. J., Ryeom, S. W., Yoon, S. S. Tags: Signal Transduction Source Type: research
Differential Expression of OATP1B3 Mediates Unconjugated Testosterone Influx
This study was undertaken to ascertain the androgen uptake kinetics, functional, and clinical relevance of de novo expression of the steroid hormone transporter OATP1B3 (SLCO1B3). Experiments testing the cellular uptake of androgens suggest that testosterone is an excellent substrate of OATP1B3 (Km = 23.2 μmol/L; Vmax = 321.6 pmol/mg/minute), and cells expressing a doxycycline-inducible SLCO1B3 construct had greater uptake of a clinically relevant concentration of 3H-testosterone (50 nmol/L; 1.6-fold, P = 0.0027). When compared with Slco1b2 (–/–) mice, Slco1b2 (–/–)/hSLCO1B3 knockins had greater ...
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Sissung, T. M., Ley, A. M., Strope, J. D., McCrea, E. M., Beedie, S., Peer, C. J., Shukla, S., van Velkinburgh, J., Reece, K., Troutman, S., Campbell, T., Fernandez, E., Huang, P., Smith, J., Thakkar, N., Venzon, D. J., Brenner, S., Lee, W., Merino, M., L Tags: Signal Transduction Source Type: research
EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion
In this study, evidence is provided that MLK3 is essential for GBM cell migration and invasion, and that an MLK inhibitor blocks EGF-induced migration and invasion. MLK3 silencing or MLK inhibition blocks EGF-induced JNK activation, suggesting that MLK3-JNK signaling promotes invasion of GBM cells. Mechanistically, it is demonstrated that DOCK180, a RAC1 guanine nucleotide exchange factor (GEF) overexpressed in invasive GBM cells, activates the MLK3-JNK signaling axis in a RAC1-dependent manner. In summary, this investigation identifies an EGFR–DOCK180–RAC1–MLK3–JNK signaling axis that drives gliobl...
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Misek, S. A., Chen, J., Schroeder, L., Rattanasinchai, C., Sample, A., Sarkaria, J. N., Gallo, K. A. Tags: Signal Transduction Source Type: research
Regulation of USP37 Expression by REST-Associated G9a-Dependent Histone Methylation
The deubiquitylase (DUB) USP37 is a component of the ubiquitin system and controls cell proliferation by regulating the stability of the cyclin-dependent kinase inhibitor 1B, (CDKN1B/p27Kip1). The expression of USP37 is downregulated in human medulloblastoma tumor specimens. In the current study, we show that USP37 prevents medulloblastoma growth in mouse orthotopic models, suggesting that it has tumor-suppressive properties in this neural cancer. Here, we also report on the mechanism underlying USP37 loss in medulloblastoma. Previously, we observed that the expression of USP37 is transcriptionally repressed by the RE1 sil...
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Dobson, T. H. W., Hatcher, R. J., Swaminathan, J., Das, C. M., Shaik, S., Tao, R.-H., Milite, C., Castellano, S., Taylor, P. H., Sbardella, G., Gopalakrishnan, V. Tags: Oncogenes and Tumor Suppressors Source Type: research
Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer. Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation. Aurora A kinase is activated by 2-ME in the S-phase as well as during mitosis, a...
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Sarkar, S., Brautigan, D. L., Larner, J. M. Tags: Oncogenes and Tumor Suppressors Source Type: research
p53 Maintains Baseline Expression of Multiple Tumor Suppressor Genes
In this study, we investigate the activities of p53 under normal low-stress conditions and discover that p53 is capable of maintaining the expression of a group of important tumor suppressor genes at baseline, many of which are haploinsufficient, which could contribute to p53-mediated tumor suppression. Mol Cancer Res; 15(8); 1051–62. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Pappas, K., Xu, J., Zairis, S., Resnick-Silverman, L., Abate, F., Steinbach, N., Ozturk, S., Saal, L. H., Su, T., Cheung, P., Schmidt, H., Aaronson, S., Hibshoosh, H., Manfredi, J., Rabadan, R., Parsons, R. Tags: Oncogenes and Tumor Suppressors Source Type: research
High-Affinity Internalizing Human scFv-Fc Antibody for Targeting FGFR1-Overexpressing Lung Cancer
This study reports a highly specific internalizing antibody fragment that can serve as a therapeutic targeting agent for efficient delivery of cytotoxic drugs into FGFR1-positive lung cancer cells. Mol Cancer Res; 15(8); 1040–50. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Sokolowska-Wedzina, A., Chodaczek, G., Chudzian, J., Borek, A., Zakrzewska, M., Otlewski, J. Tags: Oncogenes and Tumor Suppressors Source Type: research
miR-202 Diminishes TGF{beta} Receptors and Attenuates TGF{beta}1-Induced EMT in Pancreatic Cancer
Previous studies in our laboratory identified that 3-deazaneplanocin A (DZNep), a carbocyclic adenosine analog and histone methyl transferase inhibitor, suppresses TGFβ-induced epithelial-to-mesenchymal (EMT) characteristics. In addition, DZNep epigenetically reprograms miRNAs to regulate endogenous TGFβ1 levels via miR-663/4787-mediated RNA interference (Mol Cancer Res. 2016 Sep 13. pii: molcanres.0083.2016) (1). Although DZNep also attenuates exogenous TGFβ-induced EMT response, the mechanism of this inhibition was unclear. Here, DZNep induced miR-202-5p to target both TGFβ receptors, TGFBR1 and TGFBR...
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Mody, H. R., Hung, S. W., Pathak, R. K., Griffin, J., Cruz-Monserrate, Z., Govindarajan, R. Tags: Oncogenes and Tumor Suppressors Source Type: research
Glutamine Transporters Are Targets of Multiple Oncogenic Signaling Pathways in Prostate Cancer
Despite the known importance of androgen receptor (AR) signaling in prostate cancer, the processes downstream of AR that drive disease development and progression remain poorly understood. This knowledge gap has thus limited the ability to treat cancer. Here, it is demonstrated that androgens increase the metabolism of glutamine in prostate cancer cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, AR signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in prostate can...
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: White, M. A., Lin, C., Rajapakshe, K., Dong, J., Shi, Y., Tsouko, E., Mukhopadhyay, R., Jasso, D., Dawood, W., Coarfa, C., Frigo, D. E. Tags: Metabolism Source Type: research
Next-Generation Sequencing Analysis and Algorithms for PDX and CDX Models
This study describes a sensitive method to identify contaminating host reads in xenograft and explant DNA- and RNA-Seq data and is applicable to other forms of deep sequencing. Mol Cancer Res; 15(8); 1012–6. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Khandelwal, G., Girotti, M. R., Smowton, C., Taylor, S., Wirth, C., Dynowski, M., Frese, K. K., Brady, G., Dive, C., Marais, R., Miller, C. Tags: Genomics Source Type: research
Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
This study characterizes the role of the putative tumor suppressor ZBTB18 and its regulation by promoter hypermethylation, which appears to be a common mechanism to silence ZBTB18 in the mesenchymal subtype of GBM and provides a new mechanistic opportunity to specifically target this tumor subclass. Mol Cancer Res; 15(8); 998–1011. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Fedele, V., Dai, F., Masilamani, A. P., Heiland, D. H., Kling, E., Gätjens-Sanchez, A. M., Ferrarese, R., Platania, L., Soroush, D., Kim, H., Nelander, S., Weyerbrock, A., Prinz, M., Califano, A., Iavarone, A., Bredel, M., Carro, M. S. Tags: Chromatin, Epigenetics, and RNA Regulation Source Type: research
