Caspase-4 promotes metastasis and interferon-γ-induced pyroptosis in lung adenocarcinoma.

Caspase-4 (CASP4) is a member of the inflammatory caspase subfamily and promotes inflammation. Here, we report that CASP4 in lung adenocarcinoma cells contributes to both tumor progression via angiogenesis and tumor hyperkinesis and tumor cell killing in response to high interferon (IFN)-γ levels. We observe that elevated CASP4 expression in the primary tumor is associated with cancer progression in patients with lung adenocarcinoma.

Caspase-4 has a role in cell division in epithelial cells through actin depolymerization.

In addition to its role in pyroptosis and inflammatory cytokine maturation, caspase-4 (CASP4) also contributes to the fusion of phagosomes with lysosomes and cell migration. However, its role in cell division remains elusive. In this study, we demonstrate that CASP4 is indispensable for proper cell division in epithelial cells.

ANGPTL8 links inflammation and poor differentiation, which are characteristics of malignant renal cell carcinoma.

Inflammation is observed in many tumors, which affects metastasis, infiltration, and immune escape and causes poor differentiation of the cancer cells. However, the molecular basis underlying the relationship between inflammation and poor differentiation in tumors has not been identified. In this study, we demonstrate that angiopoietin-like protein-8 (ANGPTL8), which is induced by stress stimuli such as inflammation, is involved in the maintenance of the undifferentiated state of clear cell renal cell carcinoma (ccRCC) cells.

Angiopoietin-like protein 2 decreases peritoneal metastasis of ovarian cancer cells by suppressing anoikis resistance.

Peritoneal metastasis is a common mode of spread of ovarian cancer. Despite therapeutic advances, some patients have intractable peritoneal metastasis. Therefore, in-depth characterization of the molecular mechanism of peritoneal metastasis is a key imperative.

Soluble PD-L1 with PD-1-binding capacity exists in the plasma of patients with non-small cell lung cancer.

PD-L1 is one of the important immune checkpoint molecules that can be targeted by cancer immunotherapies. PD-L1 has a soluble form (sPD-L1) and a membrane-bound form (mPD-L1). Conventional enzyme-linked immunosorbent assay (ELISA) systems can detect sPD-L1 using anti-PD-L1 capture antibody through the antigen-antibody reaction, but cannot evaluate the quality and function of sPD-L1.

A measles virus selectively blind to signaling lymphocytic activation molecule shows anti-tumor activity against lung cancer cells.

Lung cancer cells, particularly those of non-small-cell lung cancer, are known to express Nectin-4. We previously generated a recombinant measles virus that uses Nectin-4 as its receptor but cannot bind its original principal receptor, signaling lymphocyte activation molecule (SLAM). This virus (rMV-SLAMblind) infects and kills breast cancer cells in vitro and in a subcutaneous xenograft model.

PI3K is a negative regulator of IgE production.

The production of IgE, a main player in allergic disorders such as asthma and atopic dermatitis, is strictly regulated and the serum concentrations of IgE are normally kept at a much lower level than other isotypes. We found that mice deficient for the p85alpha regulatory subunit of class IA phosphoinositide 3-kinase (PI3K) produced increasing amounts of serum IgE. Purified p85alpha-/- B cells produced more IgE than wild-type B cells in vitro in response to anti-CD40 mAb and IL-4.

Dendritic cells suppress IgE production in B cells.

Ig class switch recombination (CSR) is triggered by the engagement of CD40 on B cells by CD40 ligand on T cells. In addition, recent studies have shown that dendritic cells (DCs) are able to directly control the CSR of B cells through B lymphocyte stimulator protein [or B cell activation factor belonging to the tumor necrosis factor family] and a proliferation-inducing ligand. We examined in this study the regulatory role of DCs in CSR and demonstrate that DCs selectively suppress IgE production from B cells stimulated by CD40 and IL-4 through two different mechanisms: by direct cell-cell interaction or by soluble factors including transforming growth factor-beta and IFN-gamma.