Estrogen Receptor Signaling Pathways Involved in Invasion and Colony Formation of Androgen-Independent Prostate Cancer Cells PC-3

Lombardi, Ana Paola G.; Cavalheiro, Renan P.; Porto, Catarina S.; Vicente, Carolina Meloni

doi:10.3390/ijms22031153

Cited by 18 publications

(12 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Src family kinase inhibitor, AZD0530 and PP1, retards the progression of mouse OA by suppressing the Wnt/β-catenin signaling conduction [11]. Simultaneously, we found that PP2 pretreatment could inhibit the expression of non-phosphorylated β-catenin [12,13]. PP2 is a reversible and ATP-competitive SFK inhibitor with a biochemical half maximal inhibitory concentration (IC50) of 4 and 5 nM for Lck and Fyn, respectively [14].…”

Section: Introductionmentioning

confidence: 79%

PP2 alleviates the progression of osteoarthritis by inhibiting Wnt/β-catenin and activating TGF- β/Smad signaling

Zhang

Chen

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective Explore the effect and mechanism of Src inhibitor PP2 on knee osteoarthritis. Methods The protein expressions of Src, p-Src (y418) and p-FAK in normal and OA human chondrocytes were detected by immunofluorescence (IF). Chondrocytes from the femur and tibial plateau of 3-day-old mice were extracted and inoculated into 6-well plates. The chondrocytes were co-cultured with IL-1β and different doses of PP2, and then the degeneration of chondrocytes was observed. The OA model was induced by destabilizing medial meniscectomy in the right knee of mice; two weeks after the operation, different doses of PP2 were injected intraperitoneally. The medicine was given 3 times a week for 6 weeks, and then we took the knee cartilage of each group, and the degree of degeneration was observed. Results The levels of Src, p-Src (y418) and p-FAK in knee cartilage tissue of patients with OA were abnormally increased. After chondrocytes were co-treated with IL-1β and different doses of PP2, the results showed that PP2 could reduce the abnormal increase of β-catenin, p-β-catenin and other proteins created by IL-1β and reverse the decrease of p-Smad3, Aggrecan and collagen Ⅱ proteins. Meanwhile, intraperitoneal injection of PP2 in vivo significantly reduced the degeneration of articular cartilage. Conclusion Our data show that PP2 can inhibit Wnt/β-catenin and activate TGF-β/Smad signaling, thus protecting the cartilage of OA mice.

show abstract

Section: Introductionmentioning

confidence: 79%

PP2 alleviates the progression of osteoarthritis by inhibiting Wnt/β-catenin and activating TGF- β/Smad signaling

Zhang

Chen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…72 ERs activate both the SRC and PI3K/AKT signaling pathways, enhancing the tumorigenic potential, cell proliferation, migration, invasion and tumor formation of PC. 16 Moreover, ERs can also intersect with the HIF/ NF-kB signaling pathway in PC. 73 ERs-mediated long non-coding RNAs, including NEAT1, H19, MALAT1 and HOTAIR to promote PC development and the acquisition of the CRPC phenotype.…”

Section: Discussion Ers Promote Pc Development/progressionmentioning

confidence: 99%

“…ER enhanced the tumorigenic potential of PC by inducing rapid responses of SRC and PI3K/AKT. 16 Results of a previous study demonstrated that ERα is mainly localized in prostate stroma cells, and estrogen plays regulatory effects on the prostate adenoepithelium using paracrine pathways. 17 Results of a previous study further indicated that AR-positive human PC cell lines, including LNCaP, LAPC4 and 22Rv1 did not exhibit ER expression levels.…”

Section: Introduction Prostate Cancer and Tumor Immune Microenvironmentmentioning

confidence: 99%

Selective estrogen receptor modulators contribute to prostate cancer treatment by regulating the tumor immune microenvironment

Tong

2022

J Immunother Cancer

View full text Add to dashboard Cite

Prostate cancer (PC) has previously been established as a cold tumor and develops in an inert immunosuppressive environment. Current research focuses on altering the immune microenvironment of PC from cold to hot; thus, in the present review, the diverse roles of estrogen and estrogen receptor (ER) signaling was examined in the tumor cell and tumor immune microenvironment (TIM). We hypothesized that ERα promotes PC progression and ERβ impedes epithelial-mesenchymal transition in PC cells, while in the TIM, ERβ mediates the immunosuppressive environment, and low levels of ERα is associated with disease development. Selective estrogen receptor modulators (SERMs) or selective ER degraders play diverse roles in the regulation of ER isoforms. Patients with PC may benefit from the use of SERMs, including raloxifene, in combination with anti-PD1/PD-L1 checkpoint immunotherapy, or TGF-β or Wnt antagonists. The present review demonstrated that immunotherapy-based strategies combined with SERMs may be an option for the future of PC-targeting therapy.

show abstract

“…IL-17 can promote epithelial mesenchymal transition and tumor cell invasion by inducing the expression of MMP7 in PCa cells, disrupting the E-calmodulin/β-linked protein complex, and releasing β-linked protein [24]. Estrogen can activate the SRC and PI3K/AKT pathways through binding receptors and promote the expression of nonphosphorylated 7 Computational and Mathematical Methods in Medicine β-linked proteins, thereby enhancing PC-3 cell proliferation, migration, invasion, and tumor formation [25]. The findings suggested that PL may intervene in PCa by regulating signaling pathways and biological processes such as interleukin-17 and estrogen.…”

Section: Discussionmentioning

confidence: 99%

Pueraria lobata Potentially Treating Prostate Cancer on Single-Cell Level by Network Pharmacology and AutoDock: Clinical Findings and Drug Targets

Chen

Qin

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Background. Prostate cancer (PCa) is one of the common malignant tumors of the urological system, and metastasis often occurs in advanced stages. Chemotherapy is an effective treatment for advanced PCa but has limitations in terms of efficacy, side effects, multidrug resistance, and high treatment costs. Therefore, new treatment modalities for PCa need to be explored and improved. Methods. R language and GEO database were used to obtain differentially expressed genes for PCa single-cell sequencing. TCMSP, STITCH, SwissTargetPrediction, and PubChem databases were used to obtain the active ingredients and targets of Pueraria lobata (PL). Next, Cytoscape software was used to draw the interactive network diagram of “drug–active component–target pathway.” Based on the STRING database, the protein–protein interaction network was constructed. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were applied for the genes. Molecular docking was used to visualize the drug–target interaction via AutoDock Vina and PyMOL. Finally, prognosis-related genes were found by survival analysis, and Protein Atlas was used for validation. Results. Four active components and 31 target genes were obtained through the regulatory network of PL. Functional enrichment analysis showed that PL played a pharmacological role in the treatment of PCa by regulating the metabolic processes of reactive oxygen species, response to steroid hormones, and oxidative stress as well as IL-17 signaling pathway, PCa, and estrogen signaling pathway. Single-cell data showed that AR, MIF, HSP90B1, and MAOA genes were highly expressed, and molecular docking analysis showed that representative components had a strong affinity with receptor proteins. Survival analysis found that APOE, CA2, IGFBP3, MIF, F10, and NR3C1 could predict progression-free survival (PFS), and some of them could be validated in PCa. Conclusion. In this paper, a drug–active ingredient–target pathway network of PL at the single-cell level of PCa was constructed, and the findings revealed that it acted on genes such as AR, MIF, HSP90B1, and MAOA to regulate several biological processes and related signaling pathways to interfere with the occurrence and development of PCa. APOE, CA2, IGFBP3, MIF, F10, and NR3C1 were also important as target genes in predicting PFS.

show abstract

Estrogen Receptor Signaling Pathways Involved in Invasion and Colony Formation of Androgen-Independent Prostate Cancer Cells PC-3

Cited by 18 publications

References 45 publications

PP2 alleviates the progression of osteoarthritis by inhibiting Wnt/β-catenin and activating TGF- β/Smad signaling

PP2 alleviates the progression of osteoarthritis by inhibiting Wnt/β-catenin and activating TGF- β/Smad signaling

Selective estrogen receptor modulators contribute to prostate cancer treatment by regulating the tumor immune microenvironment

Pueraria lobata Potentially Treating Prostate Cancer on Single-Cell Level by Network Pharmacology and AutoDock: Clinical Findings and Drug Targets

Contact Info

Product

Resources

About