TSAd Plays a Major Role in Myo9b-Mediated Suppression of Malignant Pleural Effusion by Regulating TH1/TH17 Cell Response

Abstract

Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing T H 1 cells and increasing T H 17 cells. CD4 + naive T cells isolated from Myo9b 2/2 mouse spleens exhibited less T H 1 cell differentiation and more T H 17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell-specific adaptor protein (TSAd) was downregulated in Myo9b 2/2 mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b 2/2 group. Naive T cells purified from wild type mouse spleens transfected with TSAd-specific small interfering RNAs (siRNAs) also showed less T H 1 cell differentiation and more T H 17 cell differentiation than those from the siRNA control group. Furthermore, downregulation of TSAd in mice using cholesterol-conjugated TSAd-specific siRNA suppressed MPE development, decreased T H 1 cells, and increased T H 17 cells in MPE in vivo. Taken together, Myo9b deficiency suppresses MPE development not only by suppressing pleural cancer metastasis but also by regulating T H 1/T H 17 cell response via a TSAd-dependent pathway. This work suggests Myo9b and TSAd as novel candidates for future basic and clinical investigations of cancer.

Divergent iron-regulatory states contribute to heterogeneity in breast cancer aggressiveness

“…Additionally, actomyosin contractility genes upregulated in the invasive cells (Rock2, Cdc42bpa, Myo6, Myo1b, Myo9a, Myo5a, Myo9b, Myh10) would be expected to enhance motility by enabling cells to generate traction and migrate through the ECM (36)(37)(38). Myo6, Myo9a, and Myo9b have been implicated in promoting collective migration in 2D epithelial sheets (39)(40)(41), so our data supports extension of their role into 3D collective invasion as well. Intriguingly, expression of Rac1 and Rac2 was upregulated in the non-invasive phenotype.…”

“…Additionally, actomyosin contractility genes upregulated in the invasive cells (Rock2, Cdc42bpa & Cdc42bpb, Myo6, Myo1b, Myo9a, Myo5a, Myo9b, Myh10) would be expected to enhance motility by enabling cells to generate traction and migrate through the ECM (35)(36)(37). Myo6, Myo9a, and Myo9b have previously been implicated in promoting collective migration (38)(39)(40).…”

Mettl14-mediated m6A modification enhances the function of Foxp3+ regulatory T cells and promotes allograft acceptance

“…Moreover, we purified mouse spleen CD4 + naïve T cell using a CD4 + Naïve T cell Isolation Kit (#130-104-453, Miltenyi, Bergisch Gladbach, Germany) ( 18 ).…”

Interleukin 32 as a Potential Marker for Diagnosis of Tuberculous Pleural Effusion

“…An FITC annexin V apoptosis detection kit purchased from BD was used to detect the cell apoptosis fraction. Mononuclear cells isolated from TPE or macrophages differentiated from THP-1 cells were stained for flow cytometry as previously described ( 38 ) to analyze the expression of surface markers, intracellular markers, apoptosis, and proliferation incorporation using the three-laser FACSAria II system (BD Biosciences, USA). Marker staining was performed according to the manufacturer’s protocol.…”