FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer

Zhao, Zhibin; Zhu, Yanmei

doi:10.1186/s12885-023-11011-0

Cited by 14 publications

(6 citation statements)

References 49 publications

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“…Consequently, CALD1 emerges as a potential novel target for GC therapy, offering promising avenues for the development of new treatment strategies aimed at targeting this pathway to curb the aggressiveness of GC. Our bioinformatics analysis also underscored significant CALD1 expression in fibroblasts, the bulk dataset analysis showed that CALD1 was significantly positively correlated with the surface molecular expression in fibroblasts, which, alongside literature, suggests a potential interaction between CALD1 and fibroblasts in GC[ 32 , 33 ], necessitating further thorough investigation. The specific mechanism of action between CALD1 and fibroblasts in GC can be further studied as a subsequent research direction.…”

Section: Discussionsupporting

confidence: 57%

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway

Ma,

Miao,

Ding

et al. 2024

World J Gastrointest Oncol

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BACKGROUND CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors, including gastric cancer (GC), and is associated with tumor progression and immune infiltration; however, the roles and mechanisms of CALD1 in epithelial-mesenchymal transition (EMT) in GC are unknown. AIM To investigate the role and mechanism of CALD1 in GC progression, invasion, and migration. METHODS In this study, the relationship between CALD1 and GC, as well as the possible network regulatory mechanisms of CALD1, was investigated by bioinformatics and validated by experiments. CALD1-siRNA was synthesized and used to transfect GC cells. Cell activity was measured using the CCK-8 method, cell migration and invasive ability were measured using wound healing assay and Transwell assay, and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot. A GC cell xenograft model was established to verify the results of in vitro experiments. RESULTS Bioinformatics results showed that CALD1 was highly expressed in GC tissues, and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC. The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression, and a prognostic model was constructed and evaluated. The experimental results were consistent with the results of the bioinformatics analysis. The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1, with the strongest expression found in AGS and MKN45 cells. Cell activity was significantly reduced after CALD1-siRNA transfection of AGS and MKN45 cells. The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection, and the related mRNA and protein expression was altered. According to bioinformatics findings in GC samples, the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway, and was closely related to the PI3K-Akt signaling pathway. Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K, p-AKT, and p-mTOR, members of the PI3K-Akt pathway,while decreasing the expression of PTEN; PI3K-Akt inhibitor treatment decreased the expression of PI3K, p-AKT, and p-mTOR in cells overexpressing CALD1 (still higher than that in the normal group), but increased the expression of PTEN (still lower than that in the normal group). CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor. Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor. The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1, whereas the effect of overexpression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor. Animal experiments showed that tumour growth was slow after inhibition of CALD1, and the expression of some PI3K-Akt and EMT pathway proteins was altered. CONCLUSION Increased expression of CALD1 is a key factor in the progression, invasion, and metastasis of GC, which may be associated with regulating the PI3K-Akt pathway to promote EMT.

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Section: Discussionsupporting

confidence: 57%

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway

Ma,

Miao,

Ding

et al. 2024

World J Gastrointest Oncol

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“…Previous studies have shown that the main function of FGF2 is related to cell adhesion and angiogenesis, and patients with high FGF2 expression level have poor TNM stage and prognosis ( Li Y. et al, 2020 ). Zhao et al found that Twist1 was an independent factor affecting the pathological response to neoadjuvant chemotherapy for gastric cancer, and the expression of FAP in CAF was a significant factor for poor prognosis in patients with gastric cancer ( Tong et al, 2022 ; Zhao and Zhu, 2023 ). The expression of PDGFB has been reported to be closely related to tumor metastasis in patients with gastric cancer ( Han et al, 2020 ; Du et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Unraveling the prognostic significance of RGS gene family in gastric cancer and the potential implication of RGS4 in regulating tumor-infiltrating fibroblast

Yang,

Xing,

Luo

et al. 2024

Front. Mol. Biosci.

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Regulator of G-protein signaling (RGS) proteins are regulators of signal transduction mediated by G protein-coupled receptors (GPCRs). Current studies have shown that some molecules in the RGS gene family are related to the occurrence, development and poor prognosis of malignant tumors. However, the RGS gene family has been rarely studied in gastric cancer. In this study, we explored the mutation and expression profile of RGS gene family in gastric cancer, and evaluated the prognostic value of RGS expression. Then we established a prognostic model based on RGS gene family and performed functional analysis. Further studies showed that RGS4, as an independent prognostic predictor, may play an important role in regulating fibroblasts in the immune microenvironment. In conclusion, this study explores the value of RGS gene family in gastric cancer, which is of great significance for predicting the prognosis and guiding the treatment of gastric cancer.

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“…The presence of CAF-derived cells that had undergone this process worsened breast cancer tumor progression in vivo. A CAF gene signature was also associated with EMT and poor responses to neoadjuvant chemotherapy in a clinical study of gastric cancer [100]. Finally, TGFβ-expressing CAFs were associated with a chemoresistant TWIST1+ signature in hepatoblastoma.…”

Section: Emt and Cytotoxic Drugsmentioning

confidence: 91%

Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases

Mirjat,

Kashif,

Roberts

2023

IJMS

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TWIST1 is a transcription factor that is necessary for healthy neural crest migration, mesoderm development, and gastrulation. It functions as a key regulator of epithelial-to-mesenchymal transition (EMT), a process by which cells lose their polarity and gain the ability to migrate. EMT is often reactivated in cancers, where it is strongly associated with tumor cell invasion and metastasis. Early work on TWIST1 in adult tissues focused on its transcriptional targets and how EMT gave rise to metastatic cells. In recent years, the roles of TWIST1 and other EMT factors in cancer have expanded greatly as our understanding of tumor progression has advanced. TWIST1 and related factors are frequently tied to cancer cell stemness and changes in therapeutic responses and thus are now being viewed as attractive therapeutic targets. In this review, we highlight non-metastatic roles for TWIST1 and related EMT factors in cancer and other disorders, discuss recent findings in the areas of therapeutic resistance and stemness in cancer, and comment on the potential to target EMT for therapy. Further research into EMT will inform novel treatment combinations and strategies for advanced cancers and other diseases.

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FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer

Cited by 14 publications

References 49 publications

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway

Unraveling the prognostic significance of RGS gene family in gastric cancer and the potential implication of RGS4 in regulating tumor-infiltrating fibroblast

Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases

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