Role of FBXW7 in the quiescence of gefitinib-resistant lung cancer stem cells in EGFR-mutant non-small cell lung cancer.

In this study, we developed GRPs from the two NSCLC cell lines PC9 and HCC827, which express an EGFR exon 19 deletion mutation, by treatment with a high concentration of gefitinib. The GRPs from both PC9 and HCC827 cells expressed high levels of CD133 and FBXW7, but low levels of c-MYC. Cell cycle analysis demonstrated that the majority of GRPs existed in the G0/G1 phase. Knockdown of the FBXW7 gene significantly reduced the cell number of CD133-positive GRPs and reversed the cell population in the G0/G1-phase. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in gefitinib-resistant tumors of PC9 cells in mice and in 9 out of 14 tumor specimens from EGFR-mutant NSCLC patients with acquired resistance to gefitinib. These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in EGFR mutation-positive NSCLC. PMID: 31202256 [PubMed - as supplied by publisher]
Source: Bosnian Journal of Basic Medical Sciences - Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research

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This study found that this resistance is correlated to higher mEAK-7 expression in cancer cells.”Additional study authors are Fatima Haidar, Alexandra Fox, Connor Ray and Daniela Mendon ça, all from the University of Michigan.The study was supported in part by the National Institute of Dental and Craniofacial Research, and the Stuart and Barbara Padnos Research Award from the Rogel Cancer Center at the University of Michigan. The authors have no competing interests to declare.
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
Publication date: September 2019Source: Biomedicine &Pharmacotherapy, Volume 117Author(s): Yuan Yuan, Zhang Yangmei, Sun Rongrong, Li Xiaowu, Zhang Youwei, Sanyuan SunAbstractGastric cancer (GC) is one of the most lethal malignancies. Chemoresistance and metastasis are the main cause of treatment failure. Cancer stem cells (CSCs) have been proven to be essential for cancer metastasis and chemoresistance. PKCδ (protein kinase C-δ), a novel member of PKC family, has been validated as a synthetic lethal target in multiple cancers, and contributes to tyrosine kinase inhibitors (TKI) resistance in EGFR-mutant NS...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Sotrastaurin attenuates the stemness of gastric cancer cells by targeting PKCδ. Biomed Pharmacother. 2019 Jun 28;117:109165 Authors: Yuan Y, Yangmei Z, Rongrong S, Xiaowu L, Youwei Z, Sun S Abstract Gastric cancer (GC) is one of the most lethal malignancies. Chemoresistance and metastasis are the main cause of treatment failure. Cancer stem cells (CSCs) have been proven to be essential for cancer metastasis and chemoresistance. PKCδ (protein kinase C-δ), a novel member of PKC family, has been validated as a synthetic lethal target in multiple cancers, and contributes to tyrosine kina...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
In this study, it was found that let‑7 family expression was downregulated and miR‑17 family expression was upregulated in gefitinib‑resistant PC9/GR cells compared with gefitinib‑sensitive PC9 cells. The downregulation of let‑7 and upregulation of miR‑17 have significant clinical relevance to gefitinib resistance in NSCLC. Moreover, it was shown that downregulation of let‑7 and upregulation of miR‑17 promoted resistance to gefitinib by regulating the self‑renewal capability of NSCLC cells. In addition, let‑7 participated in the maintenance of stem cell characteristics by regulating the target gene MYC,...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Emily Roarty Jing Wang Fei Yang Michelle Barton Jeffrey Rosen Sendurai Mani Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ConclusionsNANOG and ALDH1 protein or mRNA expression showed improved prognosis in adenocarcinoma alone. ALDH1 expression correlated with an epithelial-like phenotype.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
Authors: Xiao Z, Sperl B, Gärtner S, Nedelko T, Stacher-Priehse E, Ullrich A, Knyazev PG Abstract The lung cancer stem cell (LuCSC) model comprises an attractive framework to explore acquired drug resistance in non-small cell lung cancer (NSCLC) treatment. Here, we used NSCLC cell line model to translate cellular heterogeneity into tractable populations to understand the origin of lung cancers and drug resistance. The epithelial LuCSCs, presumably arising from alveolar bipotent stem/progenitor cells, were lineage naïve, noninvasive, and prone to creating aggressive progeny expressing AT2/AT1 markers. LuCS...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
In conclusion, the hair cycle of Angora rabbits is characterized by an anagen phase between days 0 and 110, a catagen phase between days 120 and 130, and a telogen phase between days 140 and 150. FIGURE 1 Figure 1. Hair follicle synchronization model in Angora rabbits. (A) Measurement of length of the hair coat after shaving the dorsal area of Angora rabbits. (B) HE staining of sequential skin samples after shaving the dorsal area of rabbits. The anagen, catagen, telogen, and subsequent anagen stages were determined based on the histomorphology of hair follicles. Differentially Expressed lncRNAs, mRNAs, mi...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In this study, an animal model with a single BmPer gene product was selected to investigate the effect of Per-KD on the cell cycle and avoid the interaction of multiple Per expression products. There have been no previous reports of cell cycle changes after simultaneous knockdown or knockout of all mPer genes. A slow growing developmental model expressing a single BmPer gene that was continually knocked down in BmN cells (Per-KD) was used in this study. The BmN cells were free of endocrine influences. We compared cell proliferation and programmed cell death (PCD) and investigated the regulatory mechanisms in mutant and wil...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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