BSA-bounded p-cresyl sulfate potentiates the malignancy of bladder carcinoma by triggering cell migration and EMT through the ROS/Src/FAK signaling pathway

Peng, Yu‐Sen; Syu, Jhih-Pu; Wang, Sheng‐De; Pan, Pie-Chun; Kung, Hsiu‐Ni

doi:10.1007/s10565-019-09509-0

Cited by 17 publications

(13 citation statements)

References 75 publications

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“…However, tumor metastasis involves numerous factors, such as cytokines and the internal microenvironment, and EMT may be one of the most important factors in the overall process (38). Tumor cells collected from bone metastases in patients with prostate, breast and colon cancer expressed EMT markers, and those with ovarian cancer showed EMT in the process of metastasis (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Huang

2020

Mol Med Rep

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The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is primarily due to the invasive and metastatic behaviors of this disease. Laminin-332 (LM-332) is a key component of the basement membrane barrier, and is associated with tumor metastasis. The present study provides evidence towards the potential function of LM-332 in carcinoma, indicating the distinct roles of the three LM-332 subunits (α3, β3 and γ2) in cell proliferation, migration, invasion, apoptosis and the epithelial-to-mesenchymal transition (EMT) in cancer. The roles of the α3, β3 and γ2 subunits in the malignant biological behavior of PDAC were investigated in the present study. It was revealed that the α3, β3 and γ2 subunits were upregulated in PDAC. Inhibition of all LM-332 subunits abrogated the tumorigenic outcomes, which included cell proliferation, apoptosis, invasion, migration and EMT in vitro. However, the three LM-332 subunits had different degrees of effects on biological behavior. It was observed that LAMA3 (α3) had a stronger effect on cell proliferation, migration and invasion. In addition, LAMB3 (β3) knockdown significantly increased E-cadherin levels and decreased vimentin levels, indicating that LAMB3 was associated with EMT. Likewise, LAMC2 (γ2) mediated proliferation, apoptosis, invasion and migration. However, small interfering (si)-LAMC2 promoted the progression of EMT, which was the opposite effect to that of si-LAMB3. The LM-332 subunits (α3, β3 and γ2) may be novel therapeutic targets of PDAC in the future.

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Section: Discussionmentioning

confidence: 99%

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Huang

2020

Mol Med Rep

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“…During the ROS generation process, the EMT is also affected by the regulation of Src and FAK, resulting in tumor cell migration. Studies have found that para-cresyl sulfate can promote tumor cell migration by activating ROS/Src/FAK signaling in bladder cancer tumor cells[ 212 ]. Goulet et al[ 213 , 214 ] found that IL6 can regulate cancer-associated fibroblast-induced EMT through the STAT3/AKT signaling pathway in bladder cancer, induce myeloma cell proliferation through Src, and regulate the Src/STAT3 signaling pathway in lymphatic endothelial cells.…”

Section: Impact Of Ros From Pdt On Cscsmentioning

confidence: 99%

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Zhang

Wang

et al. 2020

WJSC

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Photodynamic therapy (PDT) is an effective and promising cancer treatment. PDT directly generates reactive oxygen species (ROS) through photochemical reactions. This oxygen-dependent exogenous ROS has anti-cancer stem cell (CSC) effect. In addition, PDT may also increase ROS production by altering metabolism, endoplasmic reticulum stress, or potential of mitochondrial membrane. It is known that the half-life of ROS in PDT is short, with high reactivity and limited diffusion distance. Therefore, the main targeting position of PDT is often the subcellular localization of photosensitizers, which is helpful for us to explain how PDT affects CSC characteristics, including differentiation, self-renewal, apoptosis, autophagy, and immunogenicity. Broadly speaking, excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA, change mitochondrial permeability, activate unfolded protein response, autophagy, and CSC resting state. Therefore, understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis. In this article, we review the effects of two types of photochemical reactions on PDT, the metabolic processes, and the biological effects of ROS in different subcellular locations on CSCs.

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“…Several reports have shown that ROS cause changes in downstream molecular such as Src, FAK and 15-PGDH, leading to the activation of EMT in multiple tumors ( Wang et al, 2018 ; Cheung et al, 2020 ; Peng et al, 2020 ). Interestingly, the process of ferroptosis was often accompanied by an increase in ROS level and a decrease in the antioxidant system ( Zheng and Conrad, 2020 ; Yao et al, 2021a ).…”

Section: Resultsmentioning

confidence: 99%

Single-Cell RNA-Seq Reveals the Promoting Role of Ferroptosis Tendency During Lung Adenocarcinoma EMT Progression

Yao

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Epithelial-mesenchymal transition (EMT) and ferroptosis are two important processes in biology. In tumor cells, they are intimately linked. We used single-cell RNA sequencing to investigate the regulatory connection between EMT and ferroptosis tendency in LUAD epithelial cells. We used Seurat to construct the expression matrix using the GEO dataset GSE131907 and extract epithelial cells. We found a positive correlation between the trends of EMT and ferroptosis tendency. Then we used SCENIC to analyze differentially activated transcription factors and constructed a molecular regulatory directed network by causal inference. Some ferroptosis markers (GPX4, SCP2, CAV1) were found to have strong regulatory effects on EMT. Cell communication networks were constructed by iTALK and implied that Ferro_High_EMT_High cells have a higher expression of SDC1, SDC4, and activation of LGALS9-HARVCR2 pathways. By deconvolution of bulk sequencing, the results of CIBERSORTx showed that the co-occurrence of ferroptosis tendency and EMT may lead to tumor metastasis and non-response to immunotherapy. Our findings showed there is a strong correlation between ferroptosis tendency and EMT. Ferroptosis may have a promotive effect on EMT. High propensities of ferroptosis and EMT may lead to poor prognosis and non-response to immunotherapy.

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BSA-bounded p-cresyl sulfate potentiates the malignancy of bladder carcinoma by triggering cell migration and EMT through the ROS/Src/FAK signaling pathway

Cited by 17 publications

References 75 publications

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Single-Cell RNA-Seq Reveals the Promoting Role of Ferroptosis Tendency During Lung Adenocarcinoma EMT Progression

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