Exosome Released FZD10 Increases Ki-67 Expression via Phospho-ERK1/2 in Colorectal and Gastric Cancer

Scavo, Maria Principia; Rizzi, Federica; Depalo, Nicoletta; Armentano, Ricardo L.; Coletta, Sergio; Serino, Grazia; Fanizza, Elisabetta; Pesole, Pasqua Letizia; Cervellera, Alessandra; Carella, Nicola; Curri, Maria Lucia; Giannelli, Gianluigi

doi:10.3389/fonc.2021.730093

Cited by 16 publications

(12 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ki-67 nucleoprotein is an indicator of cell growth fraction and a marker-related to cell proliferation activity [ 22 ]. Previous studies have demonstrated that Ki-67 expression was related with proliferation and metastasis of CRC [ 23 , 24 ]. In our study, FGF12 knockdown decreased the expression of Ki-67 in vivo and in vitro experiments.…”

Section: Discussionmentioning

confidence: 99%

Depletion of Fibroblast Growth Factor 12 Restrains the Viability, Stemness, and Motility of Colorectal Cancer

Gao

Liao

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

Background. Colorectal cancer (CRC) is a leading cause of cancer-related death. CRC patients have a poor prognosis due to tumor metastasis and recurrence. Fibroblast growth factor 12 (FGF12), a member of the FGF family, is highly expressed in several cancers. However, little is known about the roles of FGF12 in CRC progression. Methods. The overall survival (OS) of CRC patients was detected via Kaplan–Meier analysis. The FGF12 expression in both CRC tissues and cells was analyzed by qRT-PCR, immunohistochemistry (IHC), and western blotting (WB). LoVo and SW480 cells were transfected with shFGF12 lentivirus to silence FGF12. In vivo and in vitro experiments were performed to explore the FGF12 functions in CRC, including CCK-8, Edu, flow cytometry, Transwell, EMT, cancer stemness, and tumor xenograft experiments. Results. FGF12 was upregulated in both CRC cells and tissues. High expression of FGF12 indicated a shorter OS in CRC patients. FGF12 knockdown inhibited the proliferation, invasion, stemness, and EMT of CRC cells. FGF12 knockdown promoted CRC cell apoptosis in vitro. 740 Y-P (a PI3K/AKT pathway activator) restored the proliferation, stemness, invasion, and EMT in FGF12-deficient cells and reversed LoVo cell apoptosis induced by FGF12 depletion. Depletion of FGF12 inhibited tumor growth, EMT, cancer stemness, and PI3K/AKT pathway in a xenograft mouse model. Conclusions. FGF12 predicts bad clinical outcome and modulates the viability, stemness, and motility of CRC cells. Our study may provide a new insight for the diagnosis and treatment of CRC.

show abstract

Section: Discussionmentioning

confidence: 99%

Depletion of Fibroblast Growth Factor 12 Restrains the Viability, Stemness, and Motility of Colorectal Cancer

Gao

Liao

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Ki-67 is closely related to cell proliferation and ribosome transcription and is often used to assess the level of tumor proliferation. If the gastric mucosa expresses Ki-67, it indicates the occurrence of Dys[ 22 ]. XJZ improved the general condition of GPL rats, reduced the degree of gastric mucosal injury and pathology, inhibited CDX-2 and Ki-67 expressions in gastric mucosa, adjusted serum MDA and SOD levels associated with oxidative stress injury, and protected the gastric mucosal barrier.…”

Section: Discussionmentioning

confidence: 99%

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

Zhang¹,

Bao²,

Chen³

et al. 2023

World J Gastrointest Oncol

View full text Add to dashboard Cite

BACKGROUND Gastric precancerous lesions (GPL) precede the development of gastric cancer (GC). They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation, bacterial infection, and injury. Abnormalities in autophagy and glycolysis affect GPL progression, and their effective regulation can aid in GPL treatment and GC prevention. Xiaojianzhong decoction (XJZ) is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL. However, its specific mechanism of action is still unclear. AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs. METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk. The rats’ body weight was monitored every 2 wk starting from the beginning of modeling. Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining. Autophagy was observed using transmission electron microscopy. The expressions of autophagy, hypoxia, and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence. The expressions of the following proteins in gastric tissues: B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3 (Bnip-3), microtubule associated protein 1 light chain 3 (LC-3), moesin-like BCL2-interacting protein 1 (Beclin-1), phosphatidylinositol 3-kimase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), p53, AMP-activated protein kinase (AMPK), and Unc-51 like kinase 1 (ULK1) were detected using western blot. The relative expressions of autophagy, hypoxia, and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction. RESULTS Treatment with XJZ increased the rats’ body weight and improved GPL-related histopathological manifestations. It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3, Beclin-1, and LC-3II expressions, resulting in inhibition of autophagy. Moreover, XJZ down-regulated glycolysis-related monocarboxylate transporter (MCT1), MCT4, and CD147 expressions. XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia, activating the PI3K/AKT/mTOR pathway, inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation. In addition, XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression. CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/ AMP...

show abstract

“…FZD10 is among the genes that are aberrantly expressed in the Wnt signaling pathway. Previous studies have shown that FZD10 is involved in the progression of several types of cancer, including colorectal cancer, gastric cancer, and synovial sarcomas ( 39 – 41 ). Additionally, a therapeutic targeting FZD10 (OTSA101) is currently in clinical trials ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling revealed FZD10 as a novel biomarker for nasopharyngeal carcinoma recurrence

Tulalamba

Ngernsombat²,

Larbcharoensub³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

BackgroundNasopharyngeal carcinoma (NPC) is a type of cancers that develops in the nasopharynx, the very upper part of the throat behind the nose. NPC is typically diagnosed in later stages of the disease and has a high rate of recurrence due to the location of the tumor growth site. In this study, we compared the gene expression profiles of NPC tissues from patients with and without recurrence to identify potential molecular biomarkers of NPC recurrence.MethodsMicroarrays were used to analyze the expression of genes in 15 NPC tissues taken at the time of diagnosis and at the site of recurrence following therapeutic treatment. Pathway enrichment analysis was used to examine the biological interactions between the major differentially expressed genes. The target identified was then validated using immunohistochemistry on 86 NPC tissue samples.ResultsOur data showed that the Wnt signaling pathway was enhanced in NPC tissues with recurrence. FZD10, a component of the Wnt signaling pathway, was significantly expressed in NPC tissues, and was significantly associated with NPC recurrence.ConclusionOur study provides new insights into the pathogenesis of NPC and identifies FZD10 as a potential molecular biomarker for NPC recurrence. FZD10 may be a promising candidate for NPC recurrence and a potential therapeutic target.

show abstract

Exosome Released FZD10 Increases Ki-67 Expression via Phospho-ERK1/2 in Colorectal and Gastric Cancer

Cited by 16 publications

References 48 publications

Depletion of Fibroblast Growth Factor 12 Restrains the Viability, Stemness, and Motility of Colorectal Cancer

Depletion of Fibroblast Growth Factor 12 Restrains the Viability, Stemness, and Motility of Colorectal Cancer

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

Transcriptomic profiling revealed FZD10 as a novel biomarker for nasopharyngeal carcinoma recurrence

Contact Info

Product

Resources

About