AMPK Activation by ASP4132 Inhibits Non-small Cell Lung Cancer Cell Growth

In primary NSCLC cells and established cell lines ASP4132 potently inhibited cell growth, proliferation and cell cycle progression as well as cell migration and invasion.
[Cell Death & Disease]
Xia, Y., Zha, J., Sang, Y.-H., Yin, H., Xu, G., Zhen, J., Zhang, Y., & Yu, B. (2021). AMPK activation by ASP4132 inhibits non-small cell lung cancer cell growth. Cell Death & Disease, 12(4), 1–14. https://doi.org/10.1038/s41419-021-03655-2 Cite
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C3G Downregulation Induces the Acquisition of a Mesenchymal Phenotype That Enhances Aggressiveness of Glioblastoma Cells

The authors report that C3G downregulation promoted the acquisition of a more mesenchymal phenotype that enhanced the migratory and invasive capacity of glioblastoma cells.
[Cell Death & Disease]
Manzano, S., Gutierrez-Uzquiza, A., Bragado, P., Sequera, C., Herranz, Ó., Rodrigo-Faus, M., Jauregui, P., Morgner, S., Rubio, I., Guerrero, C., & Porras, A. (2021). C3G downregulation induces the acquisition of a mesenchymal phenotype that enhances aggressiveness of glioblastoma cells. Cell Death & Disease, 12(4), 1–17. https://doi.org/10.1038/s41419-021-03631-w Cite
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Roche Receives Positive CHMP Opinion for Tecentriq as a First-Line Monotherapy Treatment for People with a Type of Metastatic Non-Small Cell Lung Cancer

Roche announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of Tecentriq® as a first-line treatment for adults with metastatic non-small cell lung cancer whose tumors have high PD-L1 expression, with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.
[Roche]
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Quantifying Single-Cell ERK Dynamics in Colorectal Cancer Organoids Reveals EGFR as an Amplifier of Oncogenic MAPK Pathway Signaling

To elucidate the interplay between epidermal growth factor signaling and extracellular-regulated kinase activation in tumors, scientists used patient-derived organoids from KRAS and BRAF mutant colorectal cancer.
[Nature Cell Biology]
Ponsioen, B., Post, J. B., Buissant des Amorie, J. R., Laskaris, D., van Ineveld, R. L., Kersten, S., Bertotti, A., Sassi, F., Sipieter, F., Cappe, B., Mertens, S., Verlaan-Klink, I., Boj, S. F., Vries, R. G. J., Rehmann, H., Vandenabeele, P., Riquet, F. B., Trusolino, L., Bos, J. L., & Snippert, H. J. G. (2021). Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-021-00654-5 Cite
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Faciogenital Dysplasia 5 Supports Cancer Stem Cell Traits in Basal-Like Breast Cancer by Enhancing EGFR Stability

Scientists performed the basal-like breast cancers (BLBC) tissue microarray–based immunohistochemical analysis and showed that Faciogenital Dysplasia 5 (FGD5) abundance is associated with poor prognosis in BLBCs. FGD5 deletion decreased the proliferation, invasion, and tumorsphere formation capacity of BLBC cells.
[Science Translational Medicine]
Li, K., Zhang, T., Zhao, C., Wang, F., Cui, B., Yang, Z., Lv, X., Yeerjiang, Z., Yuan, Y., Yu, J., Wang, Z., Zhang, X., Yu, J., Liu, S., Shang, S., Huang, B., Hua, F., & Hu, Z. (2021). Faciogenital Dysplasia 5 supports cancer stem cell traits in basal-like breast cancer by enhancing EGFR stability. Science Translational Medicine, 13(586). https://doi.org/10.1126/scitranslmed.abb2914 Cite
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CRISPR Screens Identify Tumor‐Promoting Genes Conferring Melanoma Cell Plasticity and Resistance

Using a CRISPR activation screening, scientists identified genes involved in BRAF inhibitor (BRAFi) resistance in cutaneous melanoma. Their upregulation promoted tumour growth of therapy‐naïve melanoma cells and BRAFi‐resistance.
[EMBO Molecular Medicine]
CRISPR screens identify tumor‐promoting genes conferring melanoma cell plasticity and resistance | EMBO Molecular Medicine. (n.d.). Retrieved March 22, 2021, from https://www.embopress.org/doi/full/10.15252/emmm.202013466 Cite
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Musashi-2 (MSI2) Regulates Epidermal Growth Factor Receptor (EGFR) Expression and Response to EGFR Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC)

Musashi-2 (MSI2) control of epidermal growth factor receptor (EGFR) expression and activity in an NSCLC cell line panel was studied using RT-PCR, Western blots, and RNA immunoprecipitation. Functional consequences of MSI2 depletion were explored for cell growth and response to EGFR-targeting drugs, in vitro and in vivo.
[Oncogenesis]
Makhov, P., Bychkov, I., Faezov, B., Deneka, A., Kudinov, A., Nicolas, E., Brebion, R., Avril, E., Cai, K. Q., Kharin, L. V., Voloshin, M., Frantsiyants, E., Karnaukhov, N., Kit, O. I., Topchu, I., Fazliyeva, R., Nikonova, A. S., Serebriiskii, I. G., Borghaei, H., … Boumber, Y. (2021). Musashi-2 (MSI2) regulates epidermal growth factor receptor (EGFR) expression and response to EGFR inhibitors in EGFR-mutated non-small cell lung cancer (NSCLC). Oncogenesis, 10(3), 1–14. https://doi.org/10.1038/s41389-021-00317-y Cite
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Uncommon Targets in Non-Small Cell Lung Cancer: Everyone Wants a Slice of Cake

In this review, scientists discuss some uncommon alterations in NSCLC such as ROS1, BRAF, RET, HER2, NTRK, MET and other targets that are in an early evaluation phase.
[Critical Reviews in Oncology/Hematology]
De Toma, A., Lo Russo, G., Signorelli, D., Pagani, F., Randon, G., Galli, G., Prelaj, A., Ferrara, R., Proto, C., Ganzinelli, M., Zilembo, N., de Braud, F., & Garassino, M. C. (2021). Uncommon targets in non-small cell lung cancer: Everyone wants a slice of cake. Critical Reviews in Oncology/Hematology, 160, 103299. https://doi.org/10.1016/j.critrevonc.2021.103299 Cite
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EGFRvIII Tumorigenicity Requires PDGFRA Co-Signaling and Reveals Therapeutic Vulnerabilities in Glioblastoma

Investigators report that EGFRvIII demonstrated a reliance on PDGFRA co-stimulatory signaling during the tumorigenic process in a genetically engineered autochthonous glioblastoma model.
[Oncogene]
Yeo, A. T., Jun, H. J., Appleman, V. A., Zhang, P., Varma, H., Sarkaria, J. N., & Charest, A. (2021). EGFRvIII tumorigenicity requires PDGFRA co-signaling and reveals therapeutic vulnerabilities in glioblastoma. Oncogene, 1–15. https://doi.org/10.1038/s41388-021-01721-9 Cite
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Circular RNA-Encoded Oncogenic E-Cadherin Variant Promotes Glioblastoma Tumorigenicity through Activation of EGFR–STAT3 Signaling

The authors report an activation mechanism of EGFR signaling in glioblastoma (GBM) by a secretory E-cadherin protein variant (C-E-Cad) encoded by a circular E-cadherin RNA through multiple-round open reading frame translation. C-E-Cad variant was overexpressed in GBM and promoted glioma stem cell tumorigenicity.
[Nature Cell Biology]
Gao, X., Xia, X., Li, F., Zhang, M., Zhou, H., Wu, X., Zhong, J., Zhao, Z., Zhao, K., Liu, D., Xiao, F., Xu, Q., Jiang, T., Li, B., Cheng, S.-Y., & Zhang, N. (2021). Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR–STAT3 signalling. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-021-00639-4 Cite
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Heterogeneity of Glial Progenitor Cells during the Neurogenesis-to-Gliogenesis Switch in the Developing Human Cerebral Cortex

The authors found that EGFR expression begins to sharply increase after gestational week 20, which corresponds to the beginning stages of human gliogenesis.
[Cell Reports]
Fu, Y., Yang, M., Yu, H., Wang, Y., Wu, X., Yong, J., Mao, Y., Cui, Y., Fan, X., Wen, L., Qiao, J., & Tang, F. (2021). Heterogeneity of glial progenitor cells during the neurogenesis-to-gliogenesis switch in the developing human cerebral cortex. Cell Reports, 34(9). https://doi.org/10.1016/j.celrep.2021.108788 Cite
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