Tumor-Associated Macrophages Drive Stromal Cell-Dependent Collagen Crosslinking and Stiffening to Promote Breast Cancer Aggression

Scientists profiled lysyl hydroxylase-mediated and lysyl oxidase-mediated collagen crosslinks and quantified the greatest abundance of total and complex collagen crosslinks in aggressive human breast cancer subtypes with the stiffest stroma.
[Nature Materials]
Maller, O., Drain, A. P., Barrett, A. S., Borgquist, S., Ruffell, B., Zakharevich, I., Pham, T. T., Gruosso, T., Kuasne, H., Lakins, J. N., Acerbi, I., Barnes, J. M., Nemkov, T., Chauhan, A., Gruenberg, J., Nasir, A., Bjarnadottir, O., Werb, Z., Kabos, P., … Weaver, V. M. (2020). Tumour-associated macrophages drive stromal cell-dependent collagen crosslinking and stiffening to promote breast cancer aggression. Nature Materials, 1–12. https://doi.org/10.1038/s41563-020-00849-5 Cite
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RON Signaling Promotes Therapeutic Resistance in ESR1 Mutant Breast Cancer

Scientists performed a proteomic kinome analysis in ESR1 Y537S mutant cells to identify hyperactivated kinases in ESR1 mutant cells. They validated Recepteur d’Origine Nantais (RON) and PI3K hyperactivity through phospho-immunoblot analysis, organoid growth assays, and in an in vivo patient-derived xenograft metastatic model.
[British Journal of Cancer]
Dustin, D., Gu, G., Beyer, A. R., Herzog, S. K., Edwards, D. G., Lin, H., Gonzalez, T. L., Grimm, S. L., Coarfa, C., Chan, D. W., Kim, B.-J., De La O, J.-P., Ellis, M. J., Liu, D., Li, S., Welm, A. L., & Fuqua, S. A. W. (2020). RON signalling promotes therapeutic resistance in ESR1 mutant breast cancer. British Journal of Cancer, 1–16. https://doi.org/10.1038/s41416-020-01174-z Cite
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Nitric Oxide-Targeted Therapy Inhibits Stemness and Increases the Efficacy of Tamoxifen in Estrogen Receptor-Positive Breast Cancer Cells

Researchers explored whether targeting nitric oxide in estrogen positive breast cancer cells impacts cancer stem cell subpopulation and sensitivity to hormonal therapy with tamoxifen.
[Laboratory Investigation]
López-Sánchez, L. M., Mena, R., Guil-Luna, S., Mantrana, A., Peñarando, J., Toledano-Fonseca, M., Conde, F., De la Haba-Rodríguez, J. R., Aranda, E., & Rodríguez-Ariza, A. (2020). Nitric oxide-targeted therapy inhibits stemness and increases the efficacy of tamoxifen in estrogen receptor-positive breast cancer cells. Laboratory Investigation, 1–12. https://doi.org/10.1038/s41374-020-00507-z Cite
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Gap Junctions Amplify Spatial Variations in Cell Volume in Proliferating Tumor Spheroids

Investigators identified that ion flow through gap junctions promoted peripheral cell swelling in loaded breast cancer model.
[Nature Communications]
McEvoy, E., Han, Y. L., Guo, M., & Shenoy, V. B. (2020). Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids. Nature Communications, 11(1), 6148. https://doi.org/10.1038/s41467-020-19904-5 Cite
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Axl and Mertk Receptors Cooperate to Promote Breast Cancer Progression by Combined Oncogenic Signaling and Evasion of Host Anti-Tumor Immunity

Scientists ablated Axl on tumor cells using CRISPR/Cas9 gene editing, and by targeting Mertk in the tumor microenvironment, they observed distinct functions of TAM as oncogenic kinases as well as inhibitory immune receptors.
[Cancer Research]
Davra, V., Kumar, S., Geng, K., Calianese, D., Mehta, D., Gadiyar, V., Kasikara, C., Lahey, K. C., Chang, Y., Wichroski, M., Gao, C., Lorenzo, M. S. D., Kotenko, S. V., Bergsbaken, T., Mishra, P. K., Gause, W. C., Quigley, M., Spires, T. E., & Birge, R. B. (2020). Axl and Mertk receptors cooperate to promote breast cancer progression by combined oncogenic signaling and evasion of host anti-tumor immunity. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-2066 Cite
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The ZNF750–RAC1 Axis as Potential Prognostic Factor for Breast Cancer

Reseachers showed that ZNF750 negatively regulates cell migration and invasion in breast cancer cells; in particular, ZNF750 binds and recruits KDM1A and HDAC1 on the LAMB3 and CTNNAL1 promoters.
[Cell Death Discovery]
Butera, A., Cassandri, M., Rugolo, F., Agostini, M., & Melino, G. (2020). The ZNF750–RAC1 axis as potential prognostic factor for breast cancer. Cell Death Discovery, 6(1), 1–9. https://doi.org/10.1038/s41420-020-00371-2 Cite
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Treatment Strategies for Breast Cancer Brain Metastases

The authors provide an overview of the therapeutic option for brain metastases from breast cancer that is currently available and outlines potential new approaches for tackling these deadly secondary tumors.
[British Journal of Cancer]
Olah, M., Menon, V., Habib, N., Taga, M. F., Ma, Y., Yung, C. J., Cimpean, M., Khairallah, A., Coronas-Samano, G., Sankowski, R., Grün, D., Kroshilina, A. A., Dionne, D., Sarkis, R. A., Cosgrove, G. R., Helgager, J., Golden, J. A., Pennell, P. B., Prinz, M., … De Jager, P. L. (2020). Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease. Nature Communications, 11(1), 6129. https://doi.org/10.1038/s41467-020-19737-2 Cite
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ppGalNAc-T4-Catalyzed O-Glycosylation of TGF-β Type Ⅱ Receptor Regulates Breast Cancer Cells Metastasis

The role of one isoform, ppGalNAc-T4, in breast cancer cell lines was investigated. The expression of ppGalNAc-T4 was found to be negatively associated with migration of breast cancer cells.
[Journal of Biological Chemistry]
Wu, Q., Zhang, C., Zhang, K., Chen, Q., Wu, S., Huang, H., Huang, T., Zhang, N., Wang, X., Li, W., Liu, Y., & Zhang, J. (2020). ppGalNAc-T4-catalyzed O-Glycosylation of TGF-β type Ⅱ receptor regulates breast cancer cells metastasis. Journal of Biological Chemistry, jbc.RA120.016345. https://doi.org/10.1074/jbc.RA120.016345 Cite
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Therapeutic Potential of PARP Inhibitors in the Treatment of Metastatic Castration-Resistant Prostate Cancer

The authors expand on the clinical development of PARP inhibitors (PARPis) in metastatic castration-resistant prostate cancer, discuss potential biomarkers that may predict successful tumor control, and summarize present and future clinical research on PARPis in the metastatic disease landscape.
[Cancers]
Jang, A., Sartor, O., Barata, P. C., & Paller, C. J. (2020). Therapeutic Potential of PARP Inhibitors in the Treatment of Metastatic Castration-Resistant Prostate Cancer. Cancers, 12(11), 3467. https://doi.org/10.3390/cancers12113467 Cite
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In Silico and In Vitro Studies on the Anti-Cancer Activity of Andrographolide Targeting Survivin in Human Breast Cancer Stem Cells

Human CD24/CD44+ breast cancer stem cells (BCSCs) were treated with andrographolide in vitro for 24 hours. The cytotoxic effect of andrographolide on BCSCs was compared to that on human mesenchymal stem cells.
[PLoS One]
Wanandi, S. I., Limanto, A., Yunita, E., Syahrani, R. A., Louisa, M., Wibowo, A. E., & Arumsari, S. (2020). In silico and in vitro studies on the anti-cancer activity of andrographolide targeting survivin in human breast cancer stem cells. PLOS ONE, 15(11), e0240020. https://doi.org/10.1371/journal.pone.0240020 Cite
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EMT Transcription Factor ZEB1 Represses the Mutagenic POLθ-Mediated End-Joining Pathway in Breast Cancers

Scientists combined a bioinformatics approach exploring both METABRIC and TCGA databases with CRISPR/Cas9-mediated depletion of the zinc finger E-box binding homeobox 1 (ZEB1) in claudin-low tumor cells or forced expression of ZEB1 in basal-like tumor cells, two TNBC subtypes, to demonstrate that ZEB1 represses DNA polymerase theta (POLθ) expression.
[Cancer Research]
Prodhomme, M. K., Pommier, R. M., Franchet, C., Fauvet, F., Bergoglio, V., Brousset, P., Morel, A.-P., Brunac, A.-C., Devouassoux-Shisheboran, M., Petrilli, V., Moyret-Lalle, C., Hoffmann, J.-S., Puisieux, A., & Tissier, A. (2020). EMT transcription factor ZEB1 represses the mutagenic POLθ-mediated end-joining pathway in breast cancers. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-2626 Cite
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