Cell adhesion molecules (CAMs) are cell surface glycoproteins mediating interactions of cells with other cells and the extracellular matrix. By mediating the adhesion and modulating activity of other plasma membrane proteins, CAMs are involved in regulating a multitude of cellular processes, including growth, proliferation, migration, and survival of cells. In this review, we present evidence showing that various CAMs interact with the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase inducing pro-proliferative and anti-apoptotic intracellular signaling in response to binding to several soluble ligands, including the epidermal growth factor. We discuss that CAMs are involved in regulating EGFR signaling by either potentiating or inhibiting the soluble ligand-dependent activation of EGFR. In addition, CAMs induce soluble ligand-independent forms of EGFR activity and regulate the levels of EGFR and its ligand-induced degradation. The CAM-dependent modulation of EGFR activity plays a key role in regulating the growth, proliferation, and survival of cells. Future research is needed to determine whether these processes can be targeted in both normal and cancerous cells by regulating interactions of EGFR with various CAMs.

Advances in stem cell (SC) technology allow the generation of cellular models that recapitulate the histological, molecular and physiological properties of humanized in vitro three dimensional (3D) models, as well as production of cell-derived therapeutics such as extracellular vesicles (EVs). Improvements in organ-on-chip platforms and human induced pluripotent stem cells (hiPSCs) derived neural/glial cells provide unprecedented systems for studying 3D personalized neural tissue modeling with easy setup and fast output. Here, we highlight the key points in differentiation procedures for neurons, astrocytes, oligodendrocytes and microglia from single origin hiPSCs. Additionally, we present a well-defined humanized neural tissue-on-chip model composed of differentiated cells with the same genetic backgrounds, as well as the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles to propose a novel treatment for neuroinflammation derived diseases. Around 100 nm CD9 + EVs promote a more anti-inflammatory and pro-remodeling of cell-cell interaction cytokine responses on tumor necrosis factor-α (TNF-α) induced neuroinflammation in neural tissue-on-chip model which is ideal for modeling authentic neural-glial patho-physiology.

The roles of gap junctions (GJs) and its components, connexins, in the autophagy of cervical cancer cells have been rarely investigated. Our previous study demonstrated that connexin 32 (Cx32) exerted an anti‑apoptotic effect on cervical cancer. However, as an important regulator of apoptosis, whether the autophagy is involved in the function of Cx32 on cervical cancer cells is not well defined. The present study aimed to investigate the role of Cx32 on autophagy and apoptosis inhibition in cervical cancer cells. The expression levels of Cx32 and the autophagy‑associated protein LC3‑Ⅱ in paracancerous cervical tissues (n=30) and cervical cancer (n=50) tissues were determined via western blotting. In total, 45 cervical cancer specimens were used to evaluate the clinical relevance of Cx32 and LC3‑Ⅱ. It was found that both Cx32 and LC3‑Ⅱ were upregulated in cervical cancer tissues compared with those in paracancerous cervical tissues. The effect of Cx32 on autophagy was examined by detecting the change of LC3‑Ⅱ using western blotting, transfection with enhanced green fluorescent protein‑LC3 plasmid and transmission electron microscopy analysis. Overexpression of Cx32 significantly enhanced autophagy in HeLa‑Cx32 cells, whereas knockdown of Cx32 suppressed autophagy in C‑33A cells. The flow cytometry results demonstrated that Cx32 inhibited the apoptosis of cervical cancer cells by promoting autophagy. Moreover, Cx32 triggered autophagy via the activation of the AMP‑activated protein kinase (AMPK) signalling, regardless of the presence or absence of GJs. Collectively, it was identified that Cx32 exerted its anti‑apoptotic effect by activating autophagy via the AMPK pathway in cervical cancer, which demonstrates a novel mechanism for Cx32 in human cervical cancer progression.

There has been increasing evidence for the vital role played by gap junction protein beta-1 (GJB1) in ovarian cancer (OC) and for the possibility of this protein serving as a therapeutic target. However, the detailed mechanism of GJB1 in OC has not yet been clearly determined. The current study aimed to establish the molecular mechanisms of the involvement of GJB1 in OC and to further predict potential drugs targeting this protein.

To better understand the molecular mechanisms of the involvement of GJB1 in OC, RNA-Seq transcriptome sequencing was performed. Then, we carried out an RNA-Seq analysis to determine the genes differentially co-expressed with GJB1. Subsequently, we carried out bioinformation methods to study the upstream regulatory transcriptional factor (TF) of GJB1. Further, the binding of FOXA1 and GJB1 promoter was tested using ChIP-qPCR. Moreover, we performed pathway enrichment to identify the downstream regulatory mechanisms of GJB1. Furthermore, potential drugs targeting GJB1 were screened using AutoDock 4.2.

We constructed the transcriptional factor FOXA1 regulatory network based on the AnimalTFDB, JASPAR, RNA-Seq, TCGA cohort and ChIP-qPCR to study the upstream regulation of GJB1. In addition, two key pathways for the involvement of GJB1 in OC-namely the "ECM-receptor interaction" and "focal adhesion" KEGG pathways-were identified. Furthermore, ZINC000005552022 was found in a screening to be a potentially promising drug targeting GJB1.

Our study results suggested that the transcriptional factor FOXA1 regulates the involvement of GJB1 in OC through ECM-receptor interaction and focal adhesion KEGG pathways, and that ZINC000005552022 may have promising potential as a drug targeting GJB1; this finding might be used to help accelerate drug development and improve the outcomes for patients with OC.

Chemoresistance is a main obstacle in ovarian cancer therapy and new treatment strategies and further information regarding the mechanism of the medication cisplatin are urgently needed. Nitric oxide has a critical role in modulating the activity of chemotherapeutic drugs. Our previous work showed that connexin32 contributed to cisplatin resistance. However, whether nitric oxide is involved in connexin32-mediated cisplatin resistance remains unknown. In this study, using A2780 and A2780 cisplatin-resistant cells, we found that S-nitroso-N-acetyl-penicillamine, a nitric oxide donor, attenuated cisplatin toxicity by decreasing gap junctions in A2780 cells. Enhancement of gap junctions using retinoic acid reversed the effects of S-nitroso-N-acetyl-penicillamine on cisplatin toxicity. In A2780 cisplatin-resistant cells, however, S-nitroso-N-acetyl-penicillamine enhanced cisplatin toxicity by decreasing connexin32 expression. Downregulation of connexin32 expression by small interfering RNA exacerbated the effects of S-nitroso-N-acetyl-penicillamine on cisplatin cytotoxicity and upregulation of connexin32 expression by pcDNA transfection reversed the effects of S-nitroso-N-acetyl-penicillamine on cisplatin cytotoxicity. Our study suggests for the first time that combining cisplatin with nitric oxide in clinical therapies for ovarian cancer should be avoided before cisplatin resistance emerges. The present study provides a productive area of further study for increasing the efficacy of cisplatin by combining cisplatin with the specific inhibitors or enhancers of nitric oxide in clinical treatment.