scholarly journals KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Gao ◽  
Ru Zhao ◽  
Junmei Liu ◽  
Wenbo Zhang ◽  
Feifei Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Growth Factor Receptor ◽  
Clinical Problem ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Castration Resistant Prostate Cancer ◽  
Egfr Signaling ◽  
Castration Resistant ◽  
Egfr Signaling Pathway

Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target.

scholarly journals Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4619
Author(s):  
Eun Yeong Lim ◽  
Joon Park ◽  
Yun Tai Kim ◽  
Min Jung Kim
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Castration Resistant Prostate Cancer ◽  
Monocyte Chemoattractant Protein 1 ◽  
Downstream Signaling ◽  
Castration Resistant

Imipramine (IMI) is a tricyclic synthetic antidepressant that is used to treat chronic psychiatric disorders, including depression and neuropathic pain. IMI also has inhibitory effects against various cancer types, including prostate cancer; however, the mechanism of its anticancer activity is not well understood. In the present study, we investigated the antimetastatic and anti-invasive effects of IMI in metastatic castration-resistant prostate cancer PC-3 cells, with an emphasis on the serine/threonine protein kinase AKT-mediated nuclear factor kappa B (NF-κB) signaling pathway. While IMI did not induce cell death, it attenuated PC-3 cell proliferation. According to the wound healing assay and invasion assay, migration and invasion in PC-3 cells were significantly inhibited by IMI in a dose-dependent manner. IMI significantly downregulated p-AKT protein expression but upregulated phospho-extracellular signal-regulated kinase (ERK1)/2 protein expression levels. Furthermore, IMI treatment resulted in decreased AKT-mediated downstream signaling, including p-inhibitor of κB kinase (IKK)α/β, p-inhibitor of κB (IκBα), and p-p65. Inhibited NF-κB signaling reduced the secretion of several proinflammatory cytokines and chemokine by PC-3 cells. Overall, our study explored the negative correlation between the use of antidepressants and prostate cancer progression, showing that IMI attenuated cell viability, migration, and invasion of PC-3 cells by suppressing the expression of AKT and NF-κB-related signaling proteins and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1).

scholarly journals Everolimus combined with gefitinib in patients with metastatic castration-resistant prostate cancer: Phase 1/2 results and signaling pathway implications

Cancer ◽  
2015 ◽  
Vol 121 (21) ◽  
pp. 3853-3861 ◽  
Author(s):  
Dana E. Rathkopf ◽  
Steven M. Larson ◽  
Aseem Anand ◽  
Michael J. Morris ◽  
Susan F. Slovin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Phase 1 ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

The ERB family receptor dimerization in glioblastoma—An eTag assay analysis of 23 cases

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1582-1582
Author(s):  
M. R. Hameed ◽  
L. Sharer ◽  
E. Cho ◽  
S. Aisner ◽  
L. Cao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Driving Forces ◽  
Growth Factor Receptor ◽  
Signaling Molecules ◽  
Egfr Signaling ◽  
Fluorescent Reporter ◽  
Downstream Signaling ◽  
Egfr Signaling Pathway ◽  
Ffpe Tumor ◽  
Her 2

1582 Background: Glioblastoma is the most malignant astrocytic tumor and accounts for about 50–60% of all astrocytic neoplasms. Despite intensive radiation and chemotherapy, less than 2% of patients survive more than 3 years. The Erb family of signaling molecules are transmembrane receptors with intrinsic kinase activity (except ErbB3) capable of modifying tyrosine residues on the receptor itself as well as on downstream signaling molecules. Under physiological conditions a variety of ligands interact and act as driving forces in the formation of homo and heterodimeric complexes between the four receptors leading to signal amplification and downstream activities. More than one third of glioblastoma cases show gene amplification of epidermal growth factor receptor (EGFR) which can be in truncated or rearranged form. The eTag assay system (Monogram) is an antibody based fluorescent assay that has the potential to assess the activation state of the EGFR signaling pathway. Methods: Twenty three cases of glioblastoma were selected for eTag analysis. There were twelve males and eleven females with ages ranging from 20–84 years. After reviewing the histology, 10 micron sections were cut from formalin fixed paraffin embedded (FFPE) tumor tissue blocks. Specific monoclonal antibodies of the Erb family bound to a fluorescent reporter (eTag) were applied to tissue sections. After binding of specific analyte, a second monoclonal antibody is added which acts as molecular scissors resulting in cleavage of “eTags”. The released eTag molecules are separated by capillary electrophoresis and measured as relative fluorescent units. Various FFPE tumor cell lines were used as controls. Results: Nineteen out of twenty three tumors (82%) showed the presence of dimers of the Erb family signaling pathway. High levels of intra and /or extracellular EGFR homodimers (HER-1-HER-1) were detected in eight samples (35%). EGFR-HER-3 dimers and EGFR-HER-2 dimers were seen at high levels in four and six samples (17% and 26% respectively). High levels of HER-2-HER3 dimers were detected in six samples (26%). Conclusion: The EGFR signaling pathway plays a substantial role in tumorigenesis of glioblastoma. Identification of receptor homo and heterodimers may be of value during treatment planning of individual patients. No significant financial relationships to disclose.

Statin inhibits the proliferation of human castration-resistant prostate cancer cells by controlling NFkB-LIN28B-let7 miRNA signaling pathway.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 269-269 ◽  
Author(s):  
Chang Wook Jeong ◽  
Ja Hyeon Ku ◽  
Hyeon Hoe Kim ◽  
Cheol Kwak ◽  
Minyong Kang
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Simvastatin Treatment ◽  
Castration Resistant

269 Background: Although statin use has been associated with improved outcomes in prostate cancer, the molecular mechanism of this action is still unclear. Based on previous findings, we aimed to investigate the potential role of NFkB-Lin28B-let7 miRNA signaling pathway in human prostate cancer, particularly, castration-resistant prostate cancer (CRPC) cells, as a molecular mechanism of statin effect. Methods: Various human CRPC cell lines (PC3, DU145, 22Rv1, C42B) were used in this study. Proliferation of prostate cancer cells were measured by MTT assay and colony formation assay. Lin28B and NF-κB expression were controlled by siRNA transfection and the expression on Lin28 and let-7 miRNA were quantitated using RT-PCR and western blotting. Results: Notably, simvastatin treatment on various CRPC cell lines decreased cell viabilities in a dose dependent manner. It also significantly inhibited cell growth in clonogenic assay. In these CRPC cells, LIN28 gene was highly expressed in mRNa and protein levels. Conversely, micro RNA (miRNA) expressions of let7 family were remarkably downregulated in CRPC cells. By simvastatin treatment, mRNA and protein level of Lin28B were decreased, while let7 miRNA expressions were restored, which was the key finding of the current study. Considering NFkB is the upstream molecule of Lin28B, we found that the double treatment of statin and NF-κB inhibitor (CAPE) resulted in decreased cell viability, Lin28B and cyclin D1 expression, synergistically. Of note, let-7 miRNA levels were restored after simvastatin treatment, and further increased their expression levels by CAPE double treatment. In order to confirm this mechanistic clue, we specifically inhibited Lin28B and NF-κB genes, respectively, resulting in increased cell apoptosis signaling in the Lin28b or NF-κB knock down cells by combined treatment with simvastatin. Conclusions: In conclusion, simvastatin inhibited the cell growth of various human CRPC cell lines by controlling NFkB-LIN28B-let7 miRNA signaling pathway, and therefore; concurrent NF-κB inhibition with simvastatin treatment induce the synergistic anti-cancer effects in human CRPC cells.

The regulation effect of EGFR signaling pathway on PD-L1 expression on esophageal squamous cell carcinoma cell lines.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15577-e15577
Author(s):  
Ran Lin Wang ◽  
Tao Li ◽  
Jianming Huang ◽  
Jiahua Lv
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Radiotherapy Alone ◽  
Pcr Method ◽  
Egfr Tki

e15577 Background: To explore the effect of radiation combined with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKI) on the expression of PD-L1 in ESCC cell lines, and to provide theoretical support for radiotherapy combined with EGFR-TKI for esophageal cancer. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) method was used to assess EGFR and PD-L1 mRNA expression on ESCC cell lines when different doses of X-ray irradiation were conducted on ESCC cell lines TE-1 and ECA-109 combining with EGFR-TKI or not. Results: In ESCC cell lines TE-1 and ECA-109, the expression of EGFR and PD-L1 mRNA was increased significantly by the activation of EGFR signaling pathway and decreased after the use of gefitinib (P > 0.01). Both EGFR (P < 0.01) and PD-L1(P < 0.01) mRNA expression of ESCC cell lines TE-1 and ECA-109 were increased by radiotherapy alone. EGFR-TKI could block the increase of both EGFR mRNA (P < 0.01) and PD-L1 mRNA (P < 0.01) which was induced by radiation. Conclusions: EGFR signaling pathway is involved in the regulation of PD-L1 expression in ESCC cell lines. Radiation could up-regulate the expression of EGFR and PD-L1 mRNA in ESCC cells which could be blocked by the use of EGFR-TKI.

scholarly journals Cotargeting Polo-Like Kinase 1 and the Wnt/β-Catenin Signaling Pathway in Castration-Resistant Prostate Cancer

2015 ◽  
Vol 35 (24) ◽  
pp. 4185-4198 ◽  
Author(s):  
Jie Li ◽  
Anju Karki ◽  
Kurt B. Hodges ◽  
Nihal Ahmad ◽  
Amina Zoubeidi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Therapeutic Option ◽  
Negative Regulator ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant

The Wnt/β-catenin signaling pathway has been identified as one of the predominantly upregulated pathways in castration-resistant prostate cancer (CRPC). However, whether targeting the β-catenin pathway will prove effective as a CRPC treatment remains unknown. Polo-like kinase 1 (Plk1) is a critical regulator in many cell cycle events, and its level is significantly elevated upon castration of mice carrying xenograft prostate tumors. Indeed, inhibition of Plk1 has been shown to inhibit tumor growth in severalin vivostudies. Here, we show that Plk1 is a negative regulator of Wnt/β-catenin signaling. Plk1 inhibition or depletion enhances the level of cytosolic and nuclear β-catenin in human prostate cancer cells. Furthermore, inhibition of Wnt/β-catenin signaling significantly potentiates the antineoplastic activity of the Plk1 inhibitor BI2536 in both cultured prostate cancer cells and CRPC xenograft tumors. Mechanistically, axin2, a negative regulator of the β-catenin pathway, serves as a substrate of Plk1, and Plk1 phosphorylation of axin2 facilitates the degradation of β-catenin by enhancing binding between glycogen synthase kinase 3β (GSK3β) and β-catenin. Plk1-phosphorylated axin2 also exhibits resistance to Cdc20-mediated degradation. Overall, this study identifies a novel Plk1-Wnt signaling axis in prostate cancer, offering a promising new therapeutic option to treat CRPC.

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