Sensitizing effect of juglone is mediated by down regulation of Notch1 signaling pathway in trastuzumab-resistant SKBR3 cells

Sajadimajd, Soraya; Yazdanparast, Razieh

doi:10.1007/s10495-016-1291-9

Cited by 19 publications

(17 citation statements)

References 33 publications

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“…Recently, a novel Pin1 inhibitor, KPT-6566, inhibits the PPIase activity and induces the degradation of Pin1 by covalently interacting with its catalytic core 38 . Moreover, inhibiting Pin1 sensitizes many cancer cells to chemotherapy, including HCC to sorafenib 228 , breast cancer to trastuzumab 229 , rapamycin 53 , Taxol and 5-fluorouracil 141 , colon cancer to Taxol 84 , and AML to retinoic acid 81 . Increasing evidence showed that Pin1 is a potential target for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy

et al. 2018

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Pin1 is the only known peptidyl-prolyl cis–trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cellular processes, the aberrance of which lead to both degenerative and neoplastic diseases. Pin1 is highly expressed in the majority of cancers and its deficiency significantly suppresses cancer progression. According to the ground-breaking summaries by Hanahan D and Weinberg RA, the hallmarks of cancer comprise ten biological capabilities. Multiple researches illuminated that Pin1 contributes to these aberrant behaviors of cancer via promoting various cancer-driving pathways. This review summarized the detailed mechanisms of Pin1 in different cancer capabilities and certain Pin1-targeted small-molecule compounds that exhibit anticancer activities, expecting to facilitate anticancer therapies by targeting Pin1.

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Section: Introductionmentioning

confidence: 99%

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy

et al. 2018

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“…8 Interestingly, Pin1 overexpression has also recently been linked to trastuzumab resistance, and inhibition of Pin1 may help sensitize resistant cells to treatment. 52 Further exploration of the relationship between Pin1, CDKs, and the Smad3/TGFb pathway in HER2C as well as triple negative disease may provide important insights into key mechanisms of treatment resistance for these aggressive breast cancer subtypes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of CDK-mediated Smad3 phosphorylation reduces the Pin1-Smad3 interaction and aggressiveness of triple negative breast cancer cells

et al. 2017

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Triple negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. Although TNBC is not defined by specific therapeutic targets, a subset of patients have tumors that overexpress cyclins. High cyclin D/E expression catalyzes CDK4/2 activity. In turn, CDK4/2 can non-canonically phosphorylate Smad3, a key TGFβ signaling intermediate, and this phosphorylation has been associated with the shift from tumor-suppressive to oncogenic TGFβ pathway action in breast oncogenesis. Additionally, CDK-mediated Smad3 phosphorylation facilitates an interaction between Smad3 and Pin1, a cis-trans isomerase that is also overexpressed in aggressive breast cancers. Treatment with CYC065, a CDK2/9 inhibitor, decreased non-canonical Smad3 phosphorylation and inhibited the Pin1-Smad3 interaction. We hypothesized that the interaction of Pin1 and Smad3, facilitated by CDK-mediated Smad3 phosphorylation, promotes TNBC cell aggressiveness. Inhibition of the Pin1-Smad3 interaction in TNBC cell lines, through depletion of Pin1 or CYC065 treatment, resulted in decreased cell migration/invasion and impeded the EMT program. Inhibition of CDK-mediated phosphorylation of Smad3 by mutagenesis also decreased cell migration, underscoring the importance of non-canonical CDK2 phosphorylation of Smad3 to enable cell motility. Pin1 depletion restored Smad3 protein levels and tumor-suppressive activity, suggesting that the Pin1-Smad3 interaction has a negative impact on canonical Smad3 action. Collectively, the data show that the Pin1-Smad3 interaction, facilitated by CDK-mediated Smad3 phosphorylation, is associated with oncogenic TGFβ signaling and breast cancer progression. Inhibition of this interaction with CYC065 treatment may provide an important therapeutic option for TNBC patients.

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“…The Notch pathway is a highly conserved cell signaling pathway that plays a pivotal role in a variety of cellular processes, including proliferation, invasiveness and drug resistance [22,23]. Moreover, Notch1 is critical in cell fate decisions in the developing nervous system and several cancer cells, whist its activation is also involved in chemoresistance processing [24,25].…”

Section: Ivyspringmentioning

confidence: 99%

ID4 Promotes Breast Cancer Chemotherapy Resistance via CBF1-MRP1 Pathway

Zhang

Song

et al. 2020

J. Cancer

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Chemo-resistance is considered a key problem in triple negative breast cancer (TNBC) chemotherapy and as such, an urgent need exists to identify its exact mechanisms. Inhibitor of DNA binding factor 4 (ID4) was reported to play diverse roles in different breast cancer molecular phenotypes. In addition, ID4 was associated with mammary carcinoma drug resistance however its functions and contributions remain insufficiently defined. The expression of ID4 in MCF-7, MCF-7/Adr and MDA-MB-231 breast cancer cell lines and patients' tissues were detected by RT-PCR, western blot and immunohistochemistry. Furthermore, TCGA database was applied to confirm these results. Edu and CCK8 assay were performed to detect the proliferation and drug resistance in breast cancer cell lines. Transwell and scratch migration assay were used to detected metastasis. Western blot, TCGA database, Immunoprecipitation (IP), Chromatin Immunoprecipitation (ChIP) and Luciferase reporter assay were used to investigate the tumor promotion mechanisms of ID4. In this study, we report that the expression levels of ID4 appeared to correlate with breast cancers subtype differentiation biomarkers (including ER, PR) and chemo-resistance related proteins (including MRP1, ABCG2, P-gp). Down-regulation of ID4 in MCF-7/Adr and MDA-MB-231 breast cancer cell lines significantly suppressed cell proliferation and invasion, however enhanced Adriamycin sensitivity. We further demonstrated that the oncogenic and chemo-resistant effects of ID4 could be mediated by binding to CBF1 promoter region though combination with MyoD1, and then the downstream target MRP1 could be activated. We reveal for the first time that ID4 performs its function via a CBF1-MRP1 signaling axis, and this finding provides a novel perspective to find potential therapeutic targets for breast cancer chemotherapy.

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Sensitizing effect of juglone is mediated by down regulation of Notch1 signaling pathway in trastuzumab-resistant SKBR3 cells

Cited by 19 publications

References 33 publications

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy

Inhibition of CDK-mediated Smad3 phosphorylation reduces the Pin1-Smad3 interaction and aggressiveness of triple negative breast cancer cells

ID4 Promotes Breast Cancer Chemotherapy Resistance via CBF1-MRP1 Pathway

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