SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front.

Tumor invasion is the hallmark of tumor malignancy. The invasive infiltration pattern of tumor cells located at the leading edge is highly correlated with metastasis and unfavorable patient outcomes. However, the regulatory mechanisms governing tumor malignancy at the invasive margin remain unclear.

Exosomal miRNA 16-5p/29a-3p from pancreatic cancer induce adipose atrophy by inhibiting adipogenesis and promoting lipolysis.

Over 80% of the patients with pancreatic ductal adenocarcinoma (PDAC) have cachexia/wasting syndrome. Cachexia is associated with reduced survival, decreased quality of life, and higher metastasis rates. Here, we demonstrate that fat loss is the earliest feature of PDAC-exosome-induced cachexia.

Resistin stimulates PC-3 prostate cancer cell growth through stimulation of SOCS3 and SOCS5 genes.

Resistin and suppressors of cytokine signaling (SOCSs) have been reported to regulate prostate cancer (PCa) cell proliferation and survival, respectively. Whether any of the SOCS molecules mediate the mitogenic effect of resistin on PCa cells is unknown. Using PC-3 human PCa cells, we found that resistin upregulates the expression of and mRNA, but not mRNA, in a dose- and time-dependent manner.

Pancreatic cancer-derived small extracellular vesical ezrin activates fibroblasts to exacerbate cancer metastasis through STAT3 and YAP-1 signaling pathways.

Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC), play an important role in tumorigenesis, metastasis, and chemoresistance. Tumor-derived small extracellular vesicles (sEVs), which mediate cell-to-cell communication between cancer cells and fibroblasts, are also critical for cancer progression and metastasis. However, it remains unclear how PDAC cell-derived sEVs activate fibroblasts, which contributes to tumor progression.

MiR-944/CISH mediated inflammation via STAT3 is involved in oral cancer malignance by cigarette smoking.

The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown.

MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer.

Background: Epigenetic silencing of retinoic acid (RA) signaling-related genes have been linked with the pathogenesis and clinical outcome in oral squamous cell carcinoma (OSCC) carcinogenesis. However, the precise mechanisms underlying the abnormal silencing of RA signaling-related genes in OSCC have not been well investigated.

Methods: Using combined analysis of genome-wide gene expression and methylation profile from 40 matched normal-tumor pairs of OSCC specimens, we found a set of retinoid signaling related genes are frequently hypermethylated and downregulated in OSCC patient samples, including alcohol dehydrogenase, iron containing 1 (ADHFE1) and aldehyde dehydrogenase 1 family, member A2 (ALDH1A2), which are the important rate-limiting enzymes in synthesis of RA.

Pancreatic cancer-derived small extracellular vesical Ezrin regulates macrophage polarization and promotes metastasis.

Small extracellular vesicles (sEVs) mediate the interaction between tumor and tumor-associated macrophages (TAMs). This study aims to demonstrate that the pancreatic ductal adenocarcinoma (PDAC)-derived sEV Ezrin (sEV-EZR) could modulate macrophage polarization and promote PDAC metastasis. We isolated PDAC-derived sEVs and plasma sEVs from PDAC patients.

MicroRNA-486-3p functions as a tumor suppressor in oral cancer by targeting DDR1.

Background: Discoidin domain receptor-1 (DDR1) tyrosine kinase is highly expressed in a variety of human cancers and involved in various steps of tumorigenesis. However, the precise mechanisms underlying the abnormal expression of DDR1 in oral squamous cell carcinoma (OSCC) has not been well investigated.

Methods: The expression of DDR1 on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry.

TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility.

Distant metastasis leads oral cancer patients into a poor survival rate and a high recurrence stage. During tumor progression, dysregulated microRNAs (miRNAs) have been reported to involve tumor initiation and modulate oral cancer malignancy. MiR-450a was significantly upregulated in oral squamous cell carcinoma (OSCC) patients without functional reports.

Thrombospondin-2 is a Highly Specific Diagnostic Marker and is Associated with Prognosis in Pancreatic Cancer.

Background: Thrombospondin-2 (TSP-2) has been reported as an early diagnostic marker for pancreatic ductal adenocarcinoma (PDAC) in Caucasian populations. This study was designed to validateTSP-2 as a diagnostic marker in a large Taiwan cohort and to investigate the association of TSP-2 with the clinical outcomes of PDAC patients.

Methods: The serum TSP-2 levels in 263 PDAC patients and 230 high-risk individuals (HRIs) were measured via an enzyme-linked immunosorbent assay.

Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation.

Parathyroid Hormone-Like Hormone (PTHLH) is an autocrine/paracrine ligand that is up-regulated in head and neck squamous cell carcinoma (HNSCC). However, the cellular function and regulatory mechanism in HNSCC remains obscure. We investigated the clinical significance of PTHLH in HNSCC patients, and verified the role of RUNX2/PTHLH axis, which is stimulated HNSCC cell growth.

MPT0B098, a Microtubule Inhibitor, Suppresses JAK2/STAT3 Signaling Pathway through Modulation of SOCS3 Stability in Oral Squamous Cell Carcinoma.

Microtubule inhibitors have been shown to inhibit Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal transduction pathway in various cancer cells. However, little is known of the mechanism by which the microtubule inhibitors inhibit STAT3 activity. In the present study, we examined the effect of a novel small-molecule microtubule inhibitor, MPT0B098, on STAT3 signaling in oral squamous cell carcinoma (OSCC).

IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma.

Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Dysregulation of SOCS protein expression in cancers can be one of the mechanisms that maintain STAT activation, but this mechanism is still poorly understood in oral squamous cell carcinoma (OSCC). Here, we report that SOCS2 protein is significantly downregulated in OSCC patients and its levels are inversely correlated with miR-424-5p expression.

RAD001-mediated STAT3 upregulation and megakaryocytic differentiation.

RAD001 is currently used as an immunosuppressant and anticancer drug. Megakaryocyte (MK) differentiation includes development from pluripotent stem cells to proliferation and differentiation toward MK formation and platelet maturation. Our preliminary assay showed that RAD001 might stimulate MK differentiation; however, the exact regulatory mechanisms needed to be elucidated.

Staurosporine induces megakaryocytic differentiation through the upregulation of JAK/Stat3 signaling pathway.

The induction of megakaryocyte (MK) differentiation is a potent strategy for the clinical treatment of diseases related to blood platelet disorders. Staurosporine (STS) is an inhibitor of protein kinase C (PKC) with an inhibitory effect on cancer cells through apoptosis induction. However, the exact mechanism of STS on MK differentiation is still unclear.