Autophagy Inhibitors Increase the Susceptibility of KRAS-Mutant Human Colorectal Cancer Cells to a Combined Treatment of 2-deoxy-D-glucose and Lovastatin

A combination of lovastatin and 2-deoxy-D-glucose synergistically reduced cell viability, arrested cells in the G2/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels.
[Acta Pharmacologica Sinica]
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An Autoregulatory Feedback Loop of miR-21/VMP1 Is Responsible for the Abnormal Expression of miR-21 in Colorectal Cancer Cells

Scientists found that the expression of miR-21 was negatively correlated with the expression of vacuole membrane protein-1 (VMP1) in colorectal cancer. Transcription of VMP1 activated either by small activating RNA or transcriptional activator GLI3 inhibited miR-21 expression through reducing its transcripts of VMP1-miR-21 and pri-miR-21, while no significant change in miR-21 expression after exogenous overexpression VMP1 in colorectal cancer cell HCT116.
[Cell Death & Disease]
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Molecular Subtype-Specific Responses of Colon Cancer Cells to the SMAC Mimetic Birinapant

Responses to the inhibitor of apoptosis protein antagonist Birinapant and oxaliplatin/5-fluorouracil were investigated in 14 colon cancer cell lines, representing the consensus molecular subtypes.
[Cell Death & Disease]
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APC Regulation of ESRP1 and p120-Catenin Isoforms in Colorectal Cancer Cells

This report describes the effects of full-length, wild-type APC (fl-APC) on cell-cell adhesion genes and p120-catenin isoform switching in SW480 colon cancer cells: fl-APC increased the expression of genes implicated in cell-cell adhesion, whereas the expression of negative regulators of E-cadherin were decreased.
[Molecular Biology of the Cell]
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Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance

Investigators used a tumor organoid model, consisting of hepatic stellate cells embedded in Collagen-1 (Col1) and colorectal cancer cell (HCT-116) spheroids, to determine the relationship between the ECM architecture, cancer cell malignancy, and chemoresistance.
[iScience]
Dominijanni, A., Devarasetty, M., & Soker, S. (2020). Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.101851 Cite
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The POLD1R689W Variant Increases the Sensitivity of Colorectal Cancer Cells to ATR and CHK1 Inhibitors

Using CRISPR/Cas9 in the colorectal cancer cell line DLD-1, which harbors four POLD1 variants, scientists established heterozygous POLD1-knockout clones with exclusive expression of distinct variants to determine the functional relevance of these variants individually by assessing their impact on ATR pathway activation, DNA replication, and cellular sensitivity to inhibition of ATR or its effector kinase CHK1.
[Scientific Reports]
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Epigenetic Activation of the Small GTPase TCL Contributes to Colorectal Cancer Cell Migration and Invasion

Myocardin-related transcription factor A (MRTF-A) promoted migration and invasion of HT-29 cells in a TC10-like (TCL)-dependent manner. MRTF-A directly bound to the proximal TCL promoter in response to hypoxia to activate TCL transcription.
[Oncogenesis]
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Berberine Inhibits Colorectal Tumor Growth by Suppressing SHH Secretion

Berberine promotes the degradation of SHH mRNA in colorectal cancer cells, interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth.
[Acta Pharmacologica Sinica]
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Checkpoint Regulator B7x Is Epigenetically Regulated by HDAC3 and Mediates Resistance to HDAC Inhibitors by Reprogramming the Tumor Immune Environment in Colorectal Cancer

Scientists found that HDAC3 regulated B7x transcription by promoting the binding of the transcription activator C/EBP-α with the B7x promoter region. Their data indicated that an antibody neutralizing B7x augmented the response to HDAC inhibitor in the colorectal cancer xenograft model and the lung metastasis model by increasing the ratios of both CD4-positive and CD8-positive T cells.
[Cell Death & Disease]
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Inhibition of Autophagy Amplifies Baicalein Induced Apoptosis in Human Colorectal Cancer

Western blot analysis of the HCT-116 cell line treated with both bacalein and chloroquine demonstrated increased expression of LC3-II, a component of autophagy. The combination of baicalein with chloroquine culminated in activation of caspase-3-mediated apoptosis.
[Molecular Therapy-Oncolytics]
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A Biosensor for the Mitotic Kinase MPS1 Reveals Spatiotemporal Activity Dynamics and Regulation

Investigators showed deregulated MPS1 signaling dynamics in colorectal cancer cell lines and tumor organoids with diverse genomic instability phenotypes.
[Current Biology]
Kuijt, T. E. F., Lambers, M. L. A., Weterings, S., Ponsioen, B., Bolhaqueiro, A. C. F., Staijen, D. H. M., & Kops, G. J. P. L. (2020). A Biosensor for the Mitotic Kinase MPS1 Reveals Spatiotemporal Activity Dynamics and Regulation. Current Biology. https://doi.org/10.1016/j.cub.2020.07.062 Cite
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