scholarly journals Integrin β8 facilitates tumor growth and drug resistance through a Y‐box binding protein 1‐dependent signaling pathway in bladder cancer

2020 ◽  
Vol 111 (7) ◽  
pp. 2423-2430
Author(s):  
Shimin Liu ◽  
Libo Chen ◽  
Heng Zhao ◽  
Qin Li ◽  
Rong Hu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Bladder Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Binding Protein ◽  
Dependent Signaling Pathway

Potent transforming activity of the small GTP-binding protein Rit in NIH 3T3 cells: evidence for a role of a p38γ-dependent signaling pathway

FEBS Letters ◽  
2001 ◽  
Vol 511 (1-3) ◽  
pp. 15-20 ◽  
Author(s):  
Kaoru Sakabe ◽  
Hidemi Teramoto ◽  
Muriel Zohar ◽  
Babak Behbahani ◽  
Hiroshi Miyazaki ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Binding Protein ◽  
3T3 Cells ◽  
Gtp Binding Protein ◽  
Gtp Binding ◽  
Transforming Activity ◽  
Nih 3T3 ◽  
Dependent Signaling Pathway ◽  
Nih 3T3 Cells

Autocrine Sonic Hedgehog Protects Multiple Myeloma Cells From Apoptosis and Enhances Drug Resistance

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2904-2904
Author(s):  
Zhiqiang Liu ◽  
Yuhuan Zheng ◽  
Haiyan Li ◽  
Yong Lu ◽  
Donna M. Weber ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Conflicts Of Interest ◽  
Myeloma Cells ◽  
Apoptosis Rate ◽  
Chemotherapy Drugs

Abstract Abstract 2904 The secreted protein sonic hedgehog (SHH) and the hedgehog signaling are of great importance in proliferation and differentiation of cells in the hematopoietic system, and also play a vital role in oncogenesis of B cell malignance. However, the functions and mechanism of SHH signaling in multiple myeloma (MM) is mostly unknown. Thus far, aberrant activation of the hedgehog signaling in tumor growth promoting and/or survival capabilities as well as a paracrine model of SHH secretion have been demonstrated in MM. In the current study, we demonstrated a new autocrine SHH functioning manner in MM cells. The Shh mRNA and the SHH protein were highly expressed both in the MM cell lines and in purified CD138+ MM cells from patients using real-time PCR, Western Blot and immunohistochemistry analyses, respectively; and the SHH protein was also detected in the culture medium. Accordingly, the Hh ligand receptor PTCH1 and PTCH2 as well as the transcriptional factor GLI1 were all overexpressed in MM cells, indicating the activation of Hh signaling pathway. Autocrine SHH played a role in MM cells survival and protected MM cells from apoptosis in vitro, and autocrine SHH accelerated xenograft tumor growth in myeloma-SCID mouse model in vivo. Moreover, autocrine SHH enhanced drug resistance of MM cells, as SHH overexpressed CAG cells (SHH+CAG) had a significantly low apoptosis rate when treated with chemotherapy drugs dexamethasone or bortezomib, as compared with wild type cells (wt-CAG). On the contrary, SHH knockdown cells (SHH-CAG) had a dramatically higher apoptosis rate. Blocking autocrine SHH ligand and treating cells with dexamethasone or bortezomib significantly improved the drug killing effect. Finally, we found that upregulated BLC2 via SHH-Gli1signaling is the signaling pathway by which MM cells enhanced the drug resistance. Our study provides a new insight into the biologic function of the autocrine SHH in proliferation, survival and the drug resistance in the myeloma cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Overexpressed circ-CEP128, a potential new circular RNA biomarker, promotes cisplatin resistance of bladder cancer cells by regulating necroptosis

2020 ◽  
Author(s):  
Ming Sun ◽  
Wenyan Zhao ◽  
Bin Zhang ◽  
Donghua Geng ◽  
Shuqiang Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cisplatin Resistance ◽  
Expression Level ◽  
Cancer Tissue ◽  
Diagnostic Biomarker ◽  
Bladder Cancer Cells

Abstract Background Bladder cancer (BC) is the most common malignancy of urinary system and cisplatin (DDP) remains the only chemotherapy option for treatment of BC at the advanced stage. The critical molecules involved in the regulation of cisplatin resistance are still largely unknown. CircRNAs has been demonstrated to be involved in tumorigenesis and development and drug resistance of various cancer cells. CircCEP128 contributed to BC progression by regulating miR-145-5p/MYD88/MAKP axis. However, functions and molecular mechanisms of circCEP128 in DDP resistance of bladder cancer cells still remain largely unclear. Methods Bladder cancer tissue and the corresponding adjacent normal tissue as well as serum samples were obtained from a total of 60 BC patients who received the same cisplatin-based chemotherapy. The expression level of circCEP128 in tissues and serums was measured using qRT-PCR. WB was utilized to detect expression level of PCNA, Cyclin D1, RIPK3, p-RIPK3, MLKL or p-MLKL. Functionally, BC cell viability and proliferation are measured through relevant experiments, including CCK8 assay and cell colony formation assay. Results In the current study, we demonstrated that circCEP128 expression was distinctly elevated in the BC tissues and serums, especially in the chemoresistant BC tissues or cell lines, correlated with poor prognosis of BC patients. In addition, ROC curve suggested that circCEP128 might serve as an effective diagnostic biomarker for BC and treatment. Furthermore, cell function assays showed that circCEP128 silencing by siRNA could reverse the drug-resistance of BC cells to cisplatin by inducing necroptosis through regulation of RIPK3/MLKL signaling pathway. Conclusions Our findings indicated that circCEP128 may serve as a valuable diagnostic biomarker in BC and contribute to cisplatin resistance of bladder cancer cells by repressing necroptosis through RIPK3/MLKL signaling pathway. These findings provide novel insights into the role of circCEP128 as a biomarker for the diagnosis and treatment target of BC.

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