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Autophagy and chemoresistance

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https://www.readbyqxmd.com/read/29305171/susd2-promotes-cancer-metastasis-and-confers-cisplatin-resistance-in-high-grade-serous-ovarian-cancer
#1
Ying Xu, Chunying Miao, Chengjuan Jin, Chunping Qiu, Yinuo Li, Xiaomei Sun, Min Gao, Nan Lu, Beihua Kong
The activation of Notch3 is associated with potential progression of ovarian cancer, tumor invasion, metastasis and chemoresistance, which account for poor prognosis of high grade serous ovarian cancer (HGSOC). However, the underlying mechanisms of Notch3 are not yet very clear. Here we show that SUSD2 is one of Notch3-regulating genes and the elevated protein expression of SUSD2 in HGSOC. We also found that its high expression level was significantly correlated with worse overall survival, early recurrence and lymph nodes metastasis...
January 2, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29296182/microrna-410-3p-attenuates-gemcitabine-resistance-in-pancreatic-ductal-adenocarcinoma-by-inhibiting-hmgb1-mediated-autophagy
#2
Junjie Xiong, Dan Wang, Ailin Wei, Nengwen Ke, Yichao Wang, Jie Tang, Sirong He, Weiming Hu, Xubao Liu
Gemcitabine-based chemotherapy is the most common treatment option for pancreatic ductal adenocarcinoma (PDAC). However, it offers little therapeutic value in many cases due to the rapid development of chemoresistance. MicroRNAs (miRNAs) have been found to play pivotal roles in the chemotherapeutic resistance of PDAC. We found that miR-410-3p was significantly down-regulated in human pancreatic cancer xenograft (HPCx) tumor tissues from gemcitabine-treated mice. Low miR-410-3p expression correlated with gemcitabine resistance in HPCx tumors and PDAC cells as well as poor prognosis in PDAC patients...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295727/mirna-409-3p-enhances-cisplatin-sensitivity-of-ovarian-cancer-cells-by-blocking-the-autophagy-mediated-by-fip200
#3
Yue Cheng, Runwu Ban, Wei Liu, Hongzhi Wang, Shuzhi Li, Zhenfei Yue, Gang Zhu, Yuan Zhuan, Changjuan Wang
Background: Efficacy of chemotherapy for ovarian cancer (OC) is usually affected by various factors,especially the chemoresistance of ovarian cancer cells. Downregulation of miR-409-3p has been found in a variety of tumors. However, the role of miR-409-3p in chemo-resistant OC cells still remains unknown. The aim of this study was to investigate the effect of miR-409-3p on cisplatin-resistant OC cells and to elucidate the mechanism by which enhances cisplatin-sensitivity of OC cells. Methods: Expression of miR-409-3p in OC cells was assessed by qRT-PCR...
January 2, 2018: Oncology Research
https://www.readbyqxmd.com/read/29290796/prlz-increases-prostate-cancer-docetaxel-resistance-by-inhibiting-lkb1-ampk-mediated-autophagy
#4
Jin Zeng, Wei Liu, Yi-Zeng Fan, Da-Lin He, Lei Li
Rationale: Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...
2018: Theranostics
https://www.readbyqxmd.com/read/29276062/targeting-urothelial-carcinoma-cells-by-combining-cisplatin-with-a-specific-inhibitor-of-the-autophagy-inducing-class-iii-ptdins3k-complex
#5
David Schlütermann, Margaretha A Skowron, Niklas Berleth, Philip Böhler, Jana Deitersen, Fabian Stuhldreier, Nora Wallot-Hieke, Wenxian Wu, Christoph Peter, Michèle J Hoffmann, Günter Niegisch, Björn Stork
BACKGROUND: Cisplatin-based regimens are routinely employed for the treatment of urothelial carcinoma. However, therapeutic success is hampered by the primary presence of or the development of cisplatin resistance. This chemoresistance is executed by multiple cellular pathways. In recent years, the cellular process of autophagy has been identified as a prosurvival pathway of cancer cells. On the one hand, autophagy enables cancer cells to survive conditions of low oxygen or nutrient supply, frequently found in tumors...
December 21, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29273065/curcumin-synergizes-with-5-fluorouracil-by-impairing-ampk-ulk1-dependent-autophagy-akt-activity-and-enhancing-apoptosis-in-colon-cancer-cells-with-tumor-growth-inhibition-in-xenograft-mice
#6
Pan Zhang, Ze-Lin Lai, Hui-Fen Chen, Min Zhang, An Wang, Tao Jia, Wen-Qin Sun, Xi-Min Zhu, Xiao-Feng Chen, Zheng Zhao, Jun Zhang
BACKGROUND: Chemoresistance is a major obstacle that limits the benefits of 5-Fluorouracil (5-Fu)-based chemotherapy for colon cancer patients. Autophagy is an important cellular mechanism underlying chemoresistance. Recent research advances have given new insights into the use of natural bioactive compounds to overcome chemoresistance in colon cancer chemotherapy. As one of the multitargeted and safer phytomedicines, curcumin has been reported to work as cancer-specific chemosensitizer, presumably via induction of autophagic signaling pathways...
December 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29259984/mtor-dependent-cell-proliferation-in-the-brain
#7
REVIEW
Larisa Ryskalin, Gloria Lazzeri, Marina Flaibani, Francesca Biagioni, Stefano Gambardella, Alessandro Frati, Francesco Fornai
The mammalian Target of Rapamycin (mTOR) is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29247711/hexokinase-2-confers-resistance-to-cisplatin-in-ovarian-cancer-cells-by-enhancing-cisplatin-induced-autophagy
#8
Xiao-Yan Zhang, Meng Zhang, Qing Cong, Ming-Xing Zhang, Meng-Yu Zhang, Ying-Ying Lu, Cong-Jian Xu
The high mortality rate of ovarian cancer is connected with the development of acquired resistance to multiple cancer drugs, especially cisplatin. Activation of cytoprotective autophagy has been implicated as a contributing mechanism for acquired cisplatin resistance in ovarian cancer cells. Hexokinase 2 (HK2) phosphorylates glucose to generate glucose-6-phosphate, the rate-limiting step in glycolysis. Higher HK2 expression has been associated with chemoresistance in ovarian cancer. However, whether HK2 functionally contributes to cisplatin resistance in ovarian cancer is unclear...
December 13, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29246644/docetaxel-mediated-autophagy-promotes-chemoresistance-in-castration-resistant-prostate-cancer-cells-by-inhibiting-stat3
#9
Fei Hu, Yu Zhao, Yi Yu, Jue-Min Fang, Ran Cui, Zhu-Qing Liu, Xian-Ling Guo, Qing Xu
Signal transducer and activator of transcription (STAT)3 expression is correlated with neoplasm growth, metastasis, and prognosis; it has also been implicated in the regulation of autophagy, which may in turn contribute to tumor chemoresistance. However, it is unknown whether STAT3 is involved in cancer cell survival in response to chemotherapy. In this study, we show that autophagy is triggered during chemotherapy and that inhibiting autophagy increased chemosensitivity of castration-resistant prostate cancer (CRPC) cells...
December 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29209153/rac3-influences-the-chemoresistance-of-colon-cancer-cells-through-autophagy-and-apoptosis-inhibition
#10
María Fernanda Rubio, María Cecilia Lira, Francisco Damián Rosa, Adrían Dario Sambresqui, María Cecilia Salazar Güemes, Mónica Alejandra Costas
Background: RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition of apoptosis and autophagy. Both mechanisms are involved in resistance to treatment with chemotherapeutic agents. The aim of this study was to investigate its role in chemoresistance of colorectal cancer. Methods: The sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells HT-29, HCT 116 and Lovo cell lines, expressing high or low natural levels of RAC3, was investigated using viability assays...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29208667/etk-interaction-with-pfkfb4-modulates-chemoresistance-of-small-cell-lung-cancer-by-regulating-autophagy
#11
Qiongyao Wang, Fanrui Zeng, Yanqin Sun, Qianqian Qiu, Jian Zhang, Weimei Huang, Jie Huang, Xiaomin Huang, Linlang Guo
PURPOSE: Epithelial and endothelial tyrosine kinase (Etk), also known as bone marrow X kinase (Bmx), was found to be critical in modulating the chemoresistance of small cell lung cancer (SCLC) in our preliminary study. However, the molecular mechanisms of Etk in SCLC chemoresistance remain poorly understood. The present study investigated the downstream factor and pathway involved. EXPERIMENTAL DESIGN: We demonstrated first that knockdown of Etk by siRNAs suppressed autophagy in chemoresistant SCLC cells, and that direct inhibition of autophagy sensitized cells to chemotherapy...
December 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29207165/combination-treatment-of-fty720-and-cisplatin-exhibits-enhanced-antitumour-effects-on-cisplatin-resistant-non-small-lung-cancer-cells
#12
Yang Li, Tinghua Hu, Tianjun Chen, Tian Yang, Hui Ren, Mingwei Chen
A major common medical treatment for lung carcinoma is cisplatin (DDP)-based therapy. However, the development or existence of chemoresistance frequently blocks its effectiveness. Currently, autophagy is recognised as a potential anticancer strategy, although there is controversy over its role in the development of cancer. In lung carcinoma, no studies of autophagy induced by FTY720, a sphingosine 1-phosphate analog and a novel immunosuppressant drug, have been published, while apoptosis has been shown to be induced by FTY720 in several cancer cell lines...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29203368/modulating-autophagy-in-cancer-therapy-advancements-and-challenges-for-cancer-cell-death-sensitization
#13
REVIEW
Punya Bhat, Jurgen Kriel, Babu Shubha Priya, Basappa Salundi, Nanjunda Swamy Shivananju, Ben Loos
Autophagy is a major protein degradation pathway capable of upholding cellular metabolism under nutrient limiting conditions, making it a valuable resource to highly proliferating tumour cells. Although the regulatory machinery of the autophagic pathway has been well characterized, accurate modulation of this pathway remains complex in the context of clinical translatability for improved cancer therapies. In particular, the dynamic relationship between the rate of protein degradation through autophagy, i.e...
December 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29187221/autophagy-maintains-the-stemness-of-ovarian-cancer-stem-cells-by-foxa2
#14
Qiaohua Peng, Jiale Qin, Yanan Zhang, Xiaodong Cheng, Xinyu Wang, Weiguo Lu, Xing Xie, Songfa Zhang
BACKGROUND: Cancer stem cells (CSCs) are regarded as the main cell type responsible for the initiation, metastasis, drug resistance, and recurrence of cancer. But the mechanism by which cancer stem cells maintain their stemness remains unclear. METHODS AND RESULTS: In the present study, ovarian cancer stem cells (OCSCs) were revealed to have an enhanced autophagic flux. Furthermore, their chemoresistance and ability to self-renewal in vitro were decreased when autophagy was inhibited by Bafilomycin A1(BafA1), Chloroquine(CQ) or autophagy related 5(ATG5) knockdown...
November 29, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29171106/autophagy-regulates-cisplatin-induced-stemness-and-chemoresistance-via-the-upregulation-of-cd44-abcb1-and-adam17-in-oral-squamous-cell-carcinoma
#15
Prajna Paramita Naik, Subhadip Mukhopadhyay, Prashanta Kumar Panda, Niharika Sinha, Chandan Kanta Das, Rajakishore Mishra, Shankargouda Patil, Sujit Kumar Bhutia
OBJECTIVE: We inspected the relevance of CD44, ABCB1 and ADAM17 in OSCC stemness and deciphered the role of autophagy/mitophagy in regulating stemness and chemoresistance. MATERIAL AND METHODS: A retrospective analysis of CD44, ABCB1 and ADAM17 with respect to the various clinico-pathological factors and their correlation was analysed in sixty OSCC samples. Furthermore, the stemness and chemoresistance were studied in resistant oral cancer cells using sphere formation assay, flow cytometry and florescence microscopy...
November 23, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29162390/opposing-functions-of-heparanase-1-and-heparanase-2-in-cancer-progression
#16
REVIEW
Israel Vlodavsky, Miriam Gross-Cohen, Marina Weissmann, Neta Ilan, Ralph D Sanderson
Heparanase, the sole heparan sulfate (HS)-degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby regulating the bioavailability of heparin-binding proteins; priming the tumor microenvironment; mediating tumor-host crosstalk; and inducing gene transcription, signaling pathways, exosome formation, and autophagy that together promote tumor cell performance and chemoresistance...
November 18, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29162158/long-noncoding-rna-malat1-regulates-autophagy-associated-chemoresistance-via-mir-23b-3p-sequestration-in-gastric-cancer
#17
Hu YiRen, Yu YingCong, You Sunwu, Li Keqin, Tong Xiaochun, Chen Senrui, Chen Ende, Lin XiZhou, Chen Yanfan
BACKGROUND: Chemoresistance has long been recognized as a major obstacle in cancer therapy. Clarifying the underlying mechanism of chemoresistance would result in novel strategies to improve patient's response to chemotherapeutics. METHODS: lncRNA expression levels in gastric cancer (GC) cells was detected by quantitative real-time PCR (qPCR). MALAT1 shRNAs and overexpression vector were transfected into GC cells to down-regulate or up-regulate MALAT1 expression...
November 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29156523/cancer-associated-%C3%AF-broblasts-confer-cisplatin-resistance-of-tongue-cancer-via-autophagy-activation
#18
Juan-Kun Liao, Bin Zhou, Xiu-Mei Zhuang, Pei-Lin Zhuang, Da-Ming Zhang, Wei-Liang Chen
Cancer-associated fibroblasts (CAFs) play important roles in carcinogenesis and progression of tongue squamous cell carcinoma (TSCC). However, effect of CAFs on chemotherapy resistance of TSCC remains largely obscure. Here, we cultured the matched primary CAFs and normal fibroblasts (NFs) pairs and detected their roles in cisplatin sensitivity of TSCC, as well as autophagy-related protein LC3 and Beclin1 expressions. During exposure to cisplatin, TSCC with CAFs group exhibited significantly increased cell viability and IC50, but reduced apoptosis than that with NFs group...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29137236/the-nucleocytoplasmic-translocation-and-up-regulation-of-ing5-protein-in-breast-cancer-a-potential-target-for-gene-therapy
#19
Xiao-Qing Ding, Shuang Zhao, Lei Yang, Xin Zhao, Gui-Feng Zhao, Shu-Peng Zhao, Zhi-Jie Li, Hua-Chuan Zheng
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130102/knockdown-of-lncrna-xist-enhances-the-chemosensitivity-of-nsclc-cells-via-suppression-of-autophagy
#20
Wei Sun, Yukun Zu, Xiangning Fu, Yu Deng
Drug resistance is the major factor contributing to the failure of chemotherapy in non-small cell lung cancer (NSCLC) patients. Emerging evidence suggests that autophagy plays a vital role in the chemoresistance of many types of tumors. However, the exact mechanism underlying the chemoresistance of NSCLC is still elusive, and it is unclear whether lncRNA-XIST is involved in autophagy and chemoresistance of NSCLC. In the present study, we demonstrated that lncRNA-XIST was overexpressed in NSCLC tumor samples, and knockdown of lncRNA-XIST significantly decreased autophagy by regulation of ATG7 as determined by qPCR and by western blotting...
December 2017: Oncology Reports
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