Differential modulation of cellular phenotype and drug sensitivity by extracellular matrix proteins in primary and metastatic pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is reported to be the third highest cause of cancer-related deaths in the United States. PDAC is known for its high proportion of stroma, which accounts for 90% of the tumor mass. The stroma is made up of extracellular matrix (ECM) and nonmalignant cells such as inflammatory cells, cancer-associated fibroblasts, and lymphatic and blood vessels.

Protein Exaptation by Endogenous Retroviral Elements Shapes Tumor Cell Senescence and Downstream Immune Signaling.

Cancer cell senescence in lung squamous cell carcinoma (LUSC) is associated with a poor response to chemotherapies and immunotherapies due to promotion of an immunosuppressive tumor microenvironment. This environment is shaped by the senescence-associated secretory pathway, which recruits suppressive immune cell populations. In a recent study, Attig and colleagues identified a transcription factor-activated molecular switch that circumvents cellular senescence through increased expression of the calbindin protein.

Epigenetically programmed resistance to chemo- and immuno-therapies.

Resistance to cancer treatments remains a major barrier in developing cancer cures. While promising combination chemotherapy treatments and novel immunotherapies have improved patient outcomes, resistance to these treatments remains poorly understood. New insights into the dysregulation of the epigenome show how it promotes tumor growth and resistance to therapy.

Inhibiting DNA methylation and RNA editing upregulates immunogenic RNA to transform the tumor microenvironment and prolong survival in ovarian cancer.

Background: Novel therapies are urgently needed for ovarian cancer (OC), the fifth deadliest cancer in women. Preclinical work has shown that DNA methyltransferase inhibitors (DNMTis) can reverse the immunosuppressive tumor microenvironment in OC. Inhibiting DNA methyltransferases activate transcription of double-stranded (ds)RNA, including transposable elements.

Nuclear mechanosensing: mechanism and consequences of a nuclear rupture.

The physical connections between the cytoskeletal system and the nucleus provide a route for the nucleus to sense the mechanical stress both inside and outside of the cell. Failure to withstand such stress leads to nuclear rupture, which is observed in human diseases. In this review, we will go through the recent findings and our current understandings of nuclear rupture.