Cancer-associated fibroblast-derived WNT5A promotes cell proliferation, metastasis, stemness and glycolysis in gastric cancer via regulating HK2.

Gastric cancer (GC) is one of the most common cancers worldwide. Tumor microenvironment plays an important role in tumor progression. This study aims to explore the role of cancer-associated fibroblasts (CAFs) in GC and the underlying mechanism. Cell viability, proliferation, invasion and migration were assessed by MTT, EdU, transwell and wound healing assays, respectively. Sphere formation assay was used to evaluate cell stemness. Glucose consumption, lactate production and ATP consumption were measured to assess glycolysis. In addition, The RNA and protein expression were detected by qRT-PCR and western blot. The interaction between wingless Type MMTV Integration Site Family, Member 5 A (WNT5A) and hexokinase 2 (HK2) was verified by Co-immunoprecipitation. The xenograft model was established to explore the function of CAFs on GC tumor growth in vivo. CAFs promoted the proliferation, metastasis, stemness and glycolysis of GC cells. WNT5A was upregulated in CAFs, and CAFs enhanced WNT5A expression in GC cells. Knockdown of WNT5A in either GC cells or CAFs repressed the progression of GC cells. In addition, WNT5A promoted HK2 expression, and overexpression of HK2 reversed the effect of WNT5A knockdown in CAFs on GC cells. Besides, knockdown of WNT5A in CAFs inhibits tumor growth in vivo. CAF-derived WNT5A facilitates the progression of GC via regulating HK2 expression.

Xu Y ，Ren Z ，Zeng F ，Yang H ，Hu C ... -  《World Journal of Surgical Oncology》

Downregulation of miRNA-214 in cancer-associated fibroblasts contributes to migration and invasion of gastric cancer cells through targeting FGF9 and inducing EMT.

Wang R ，Sun Y ，Yu W ，Yan Y ，Qiao M ，Jiang R ，Guan W ，Wang L ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Circ-PVT1/miR-106a-5p/HK2 axis regulates cell growth, metastasis and glycolytic metabolism of oral squamous cell carcinoma.

Zhu X ，Du J ，Gu Z 《-》

Upregulation of FGF9 and NOVA1 in cancer-associated fibroblasts promotes cell proliferation, invasion and migration of triple negative breast cancer.

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression. This study aimed to explore the roles of CAFs-derived Fibroblast growth factor 9 (FGF9) and Neuro-oncological ventral antigen 1 (NOVA1) in triple negative breast cancer (TNBC) progression. MDA-MB-231 and BT-549 cells were cocultured with CAF conditioned-medium (CAF-CM) or normal fibroblasts conditioned-medium (NF-CM). MTT, EdU, colony formation, wound healing, transwell migration, and invasion assays were employed to determine cell proliferation, migration and invasion, respectively. Western blot and RT-qPCR were carried out to examine the protein and mRNA expression of FGF9 and NOVA1. Xenograft tumor experiments were conducted to evaluate the effects of CAFs, FGF9, and NOVA1 on tumor growth in vivo. Our results showed that CAFs significantly promoted the proliferation, invasion, and migration of TNBC cells. FGF9 and NOVA1 were significantly upregulated in TNBC CAFs, tissues and cells. CAF-CM also could increase the expression of FGF9 and NOVA1 in TNBC cells. Knockdown of FGF9 or NOVA1 could hamper cell proliferation, invasion, migration, and EMT of TNBC cells. Moreover, CAFs with FGF9/NOVA1 knockdown also could inhibit TNBC progression. Besides, CAFs significantly accelerated tumor growth in vivo, which was blocked by FGF9/NOVA1 knockdown in nude mice. In conclusion, our results indicated the tumor-promoting role of CAFs in TNBC progression. FGF9 and NOVA1 upregulation in CAFs induced cell proliferation, migration and invasion in vitro, and facilitated tumor growth in vivo in TNBC development.

Zhang B ，Liu Y ，Yu J ，Lin X ... -  《-》

Kinesin 26B modulates M2 polarization of macrophage by activating cancer-associated fibroblasts to aggravate gastric cancer occurrence and metastasis.

The regulatory effects of KIF26B on gastric cancer (GC) have been confirmed, but the specific mechanism still needs further exploration. Pan-cancer analysis shows that the KIF26B expression is highly related to immune infiltration of cancer-associated fibroblasts (CAFs), and CAFs promote macrophage M2 polarization and affect cancers' progression. To investigate the regulatory functions of KIF26B on immune and metastasis of GC. We analyzed genes' mRNA levels by quantitative real-time polymerase chain reaction. Expression levels of target proteins were detected by immunohistochemistry, ELISA, and Western blotting. We injected AGS cells into nude mice for the establishment of a xenograft tumor model and observed the occurrence and metastasis of GC. The degree of inflammatory infiltration in pulmonary nodes was observed through hematoxylin-eosin staining. Transwell and wound healing assays were performed for the evaluation of cell invasion and migration ability. Tube formation assay was used for detecting angiogenesis. M2-polarized macrophages were estimated by immunofluorescence and flow cytometry. KIF26B was significantly overexpressed in cells and tissues of GC, and the higher expression of KIF26B was related to GC metastasis and prognosis. According to in vivo experiments, KIF26B promoted tumor formation and metastasis of GC. KIF26B expression was positively associated with CAFs' degree of infiltration. Moreover, CAFs could regulate M2-type polarization of macrophages, affecting GC cells' migration, angiogenesis, invasion, and epithelial-mesenchymal transition process. KIF26B regulated M2 polarization of macrophage through activating CAFs, regulating the occurrence and metastasis of GC.

Huang LM ，Zhang MJ 《-》