Activated Stellate Cell Paracrine HGF Exacerbated Pancreatic Cancer Cell Ferroptosis Resistance

Wu, Qiwei; Liu, Song; Guo, Yaxin; Liu, Sai; Wang, Wenyao; Liu, Huli; Gong, Aihua; Liao, Xiang; Zhu, Haitao; Wang, Dongqing

doi:10.1155/2022/2985249

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…Dysregulation of the MET/HGF pathway leads to uncontrolled cell proliferation and oncogenesis, and is observed in multiple tumor types [70]. HGF is known to exacerbate pancreatic cancer cell ferroptosis resistance [71].…”

Section: Discussionmentioning

confidence: 99%

Adverse Crosstalk between Extracellular Matrix Remodeling and Ferroptosis in Basal Breast Cancer

Desterke,

Cosialls,

Xiang

et al. 2023

Cells

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(1) Background: Breast cancer is a frequent heterogeneous disorder diagnosed in women and causes a high number of mortality among this population due to rapid metastasis and disease recurrence. Ferroptosis can inhibit breast cancer cell growth, improve the sensitivity of chemotherapy and radiotherapy, and inhibit distant metastases, potentially impacting the tumor microenvironment. (2) Methods: Through data mining, the ferroptosis/extracellular matrix remodeling literature text-mining results were integrated into the breast cancer transcriptome cohort, taking into account patients with distant relapse-free survival (DRFS) under adjuvant therapy (anthracyclin + taxanes) with validation in an independent METABRIC cohort, along with the MDA-MB-231 and HCC338 transcriptome functional experiments with ferroptosis activations (GSE173905). (3) Results: Ferroptosis/extracellular matrix remodeling text-mining identified 910 associated genes. Univariate Cox analyses focused on breast cancer (GSE25066) selected 252 individual significant genes, of which 170 were found to have an adverse expression. Functional enrichment of these 170 adverse genes predicted basal breast cancer signatures. Through text-mining, some ferroptosis-significant adverse-selected genes shared citations in the domain of ECM remodeling, such as TNF, IL6, SET, CDKN2A, EGFR, HMGB1, KRAS, MET, LCN2, HIF1A, and TLR4. A molecular score based on the expression of the eleven genes was found predictive of the worst prognosis breast cancer at the univariate level: basal subtype, short DRFS, high-grade values 3 and 4, and estrogen and progesterone receptor negative and nodal stages 2 and 3. This eleven-gene signature was validated as regulated by ferroptosis inductors (erastin and RSL3) in the triple-negative breast cancer cellular model MDA-MB-231. (4) Conclusions: The crosstalk between ECM remodeling-ferroptosis functionalities allowed for defining a molecular score, which has been characterized as an independent adverse parameter in the prognosis of breast cancer patients. The gene signature of this molecular score has been validated to be regulated by erastin/RSL3 ferroptosis activators. This molecular score could be promising to evaluate the ECM-related impact of ferroptosis target therapies in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Adverse Crosstalk between Extracellular Matrix Remodeling and Ferroptosis in Basal Breast Cancer

Desterke,

Cosialls,

Xiang

et al. 2023

Cells

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“…This signaling pathway contributes to PC resistance to iron-induced cell death. Combining antifibrotic drugs with iron death inducers has shown potential in promoting iron-induced cell death in refractory PC, providing a potential clinical therapy approach ( 80 ). Hypoxia has also been identified as a factor that reduces the sensitivity of PC cells to EGFR inhibitors through the HIF-1α-HGF-Met-PI3K-AKT PSC signaling axis.…”

Section: Drugs Targeting Pancreatic Stellate Cells For the Treatment ...mentioning

confidence: 99%

Pancreatic stellate cells in pancreatic cancer: as potential targets for future therapy

Wang¹,

He²,

Dong³

et al. 2023

Front. Oncol.

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Pancreatic cancer is a strongly malignant gastrointestinal carcinoma characterized by late detection, high mortality rates, poor patient prognosis and lack of effective treatments. Consequently, there is an urgent need to identify novel therapeutic strategies for this disease. Pancreatic stellate cells, which constitute a significant component of the mesenchymal cellular layer within the pancreatic tumor microenvironment, play a pivotal role in modulating this environment through their interactions with pancreatic cancer cells. This paper reviews the mechanisms by which pancreatic stellate cells inhibit antitumor immune responses and promote cancer progression. We also discuss preclinical studies focusing on these cells, with the goal of providing some theoretical references for the development of new therapeutic approaches for pancreatic cancer.

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Breaking the stromal barrier in pancreatic cancer: Advances and challenges

Chakkera,

Foote,

Farran

et al. 2024

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Activated Stellate Cell Paracrine HGF Exacerbated Pancreatic Cancer Cell Ferroptosis Resistance

Cited by 4 publications

References 28 publications

Adverse Crosstalk between Extracellular Matrix Remodeling and Ferroptosis in Basal Breast Cancer

Adverse Crosstalk between Extracellular Matrix Remodeling and Ferroptosis in Basal Breast Cancer

Pancreatic stellate cells in pancreatic cancer: as potential targets for future therapy

Breaking the stromal barrier in pancreatic cancer: Advances and challenges

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