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Autophagy and cancer

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https://www.readbyqxmd.com/read/29027991/n6-isopentenyladenosine-dual-targeting-of-ampk-and-rab7-prenylation-inhibits-melanoma-growth-through-the-impairment-of-autophagic-flux
#1
Roberta Ranieri, Elena Ciaglia, Giuseppina Amodio, Paola Picardi, Maria Chiara Proto, Patrizia Gazzerro, Chiara Laezza, Paolo Remondelli, Maurizio Bifulco, Simona Pisanti
Targeting the autophagic process is considered a promising therapeutic strategy in cancer since a great number of tumors, including melanoma, show high basal levels of protective autophagy that contributes to tumor progression and chemoresistance. Here, exploiting both in vitro and in vivo approaches, we identified N6-isopentenyladenosine (iPA), an end product of the mevalonate pathway, as a novel autophagy inhibitor with an interesting anti-melanoma activity. iPA, after being phosphorylated by adenosine kinase into 5'-iPA-monophosphate, induces autophagosome accumulation through AMPK activation, measured by increased fluorescent GFP-LC3 puncta and enhanced conversion into the lipidated autophagosome-associated LC3-II...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29027231/the-renaissance-of-anti-neoplastic-immunity-from-tumor-cell-demise
#2
REVIEW
Yuting Ma, Jonathan M Pitt, Qingqing Li, Heng Yang
Cancer therapies can temporarily reduce tumor burdens by inducing malignant cell death. However, cancer cure is still far from realization because tumors often gain resistance to current treatment and eventually relapse. Accumulating evidence suggests that successful cancer interventions require anti-tumor immunity. Therapy-induced cell stress responses ultimately result in one or more cell death modalities, including apoptosis, autophagy, necroptosis, and pyroptosis. These irreversible dying processes are accompanied by active or passive release of cell death-associated molecular patterns (CDAMPs), which can be sensed by corresponding pattern recognition receptors (PRR) on tumor-infiltrating immune cells...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29027230/immunogenic-stress-and-death-of-cancer-cells-contribution-of-antigenicity-vs-adjuvanticity-to-immunosurveillance
#3
REVIEW
Norma Bloy, Pauline Garcia, Céline M Laumont, Jonathan M Pitt, Antonella Sistigu, Gautier Stoll, Takahiro Yamazaki, Eric Bonneil, Aitziber Buqué, Juliette Humeau, Jan W Drijfhout, Guillaume Meurice, Steffen Walter, Jens Fritsche, Toni Weinschenk, Hans-Georg Rammensee, Cornelis Melief, Pierre Thibault, Claude Perreault, Jonathan Pol, Laurence Zitvogel, Laura Senovilla, Guido Kroemer
Cancer cells are subjected to constant selection by the immune system, meaning that tumors that become clinically manifest have managed to subvert or hide from immunosurveillance. Immune control can be facilitated by induction of autophagy, as well as by polyploidization of cancer cells. While autophagy causes the release of ATP, a chemotactic signal for myeloid cells, polyploidization can trigger endoplasmic reticulum stress with consequent exposure of the "eat-me" signal calreticulin on the cell surface, thereby facilitating the transfer of tumor antigens into dendritic cells...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29026157/bortezomib-promotes-khsv-and-ebv-lytic-cycle-by-activating-jnk-and-autophagy
#4
Marisa Granato, Maria Anele Romeo, Mariangela Sara Tiano, Roberta Santarelli, Roberta Gonnella, Maria Saveria Gilardini Montani, Alberto Faggioni, Mara Cirone
KSHV and EBV are gammaherpesviruses strictly linked to human cancers. Even if the majority of cancer cells harbor a latent infection, the few cells that undergo viral replication may contribute to the pathogenesis and maintenance of the virus-associated malignancies. Cytotoxic drugs used for the therapies of cancers harboring virus-infection often have, as side effect, the activation of viral lytic cycle. Therefore it is important to investigate whether they affect viral reactivation and understand the underlying mechanisms involved...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024815/identification-of-a-novel-autophagic-inhibitor-cepharanthine-to-enhance-the-anti-cancer-property-of-dacomitinib-in-non-small-cell-lung-cancer
#5
Zheng-Hai Tang, Wen-Xiang Cao, Xia Guo, Xiao-Yang Dai, Jia-Hong Lu, Xiuping Chen, Hong Zhu, Jin-Jian Lu
Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024631/luteoloside-induces-g0-g1-arrest-and-pro-death-autophagy-through-the-ros-mediated-akt-mtor-p70s6k-signalling-pathway-in-human-non-small-cell-lung-cancer-cell-lines
#6
Menglu Zhou, Shuying Shen, Xin Zhao, Xingguo Gong
Autophagy has attracted a great deal of interest in tumour therapy research in recent years. However, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, on autophagy remains poorly understood in human lung cells. In the present study, we have investigated the anticancer effects of luteoloside on non-small cell lung cancer (NSCLC) cells and demonstrated that luteoloside effectively inhibited cancer cell proliferation, inducing G0/G1phase arrest associated with reduced expression of CyclinE, CyclinD1 and CDK4; we further found that treatment with luteoloside did not strongly result in apoptotic cell death in NSCLC (A549 and H292) cells...
October 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29022892/the-lncrna-hulc-functions-as-an-oncogene-by-targeting-atg7-and-itgb1-in-epithelial-ovarian-carcinoma
#7
Shuo Chen, Dan-Dan Wu, Xiu-Bo Sang, Li-Li Wang, Zhi-Hong Zong, Kai-Xuan Sun, Bo-Liang Liu, Yang Zhao
Highly upregulated in liver cancer (HULC) is a long noncoding RNA (lncRNA), which has recently been identified as a key regulator in the progression of hepatocellular carcinoma, gliomas and gastric cancer. However, its role in epithelial ovarian carcinoma (EOC) remains unknown. In this study, HULC expression was examined in EOC, borderline and benign ovarian tumors, and normal ovarian tissues by RT-PCR. Ovarian cancer cell phenotypes, as well as autophagy-associated proteins were examined after HULC overexpression or downregulation by plasmid or small interfering RNA (siRNA) transfection, respectively...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022289/cloning-of-autophagy-related-micrornas
#8
Deniz Gulfem Ozturk, Muhammed Kocak, Devrim Gozuacik
Autophagy is a cellular survival pathway that is necessary for the degradation of cellular constituents such as long-lived proteins and damaged organelles. Conditions resulting in cellular stress such as starvation or hypoxia might activate autophagy. Being at the crossroads of various cellular response pathways, dysregulation of autophagy might result in pathological states including cancer and neurodegenerative diseases. Autophagy has also been shown to participate in stemness. MicroRNAs were introduced as novel regulators of autophagy, and accumulating results underlined the fact that they constituted an important layer of biological control mechanism on the autophagic activity...
October 12, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29022200/high-expression-of-the-mitophagy-related-protein-pink1-is-associated-with-a-poor-response-to-chemotherapy-and-a-poor-prognosis-for-patients-treated-with-neoadjuvant-chemotherapy-for-esophageal-squamous-cell-carcinoma
#9
Kotaro Yamashita, Hiroshi Miyata, Tomoki Makino, Yasunori Masuike, Haruna Furukawa, Koji Tanaka, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Eiichi Morii, Masaki Mori, Yuichiro Doki
BACKGROUND: Autophagy plays a major role in cellular homeostasis and is implicated in cancer progression. Damaged mitochondria are scavenged and eliminated by mitochondrial autophagy, referred to as mitophagy, which can promote cancer cell survival. This study investigated the expression and effects of the autophagy-related protein LC3 and the mitophagy-related protein Pink1 in human esophageal squamous cell carcinoma (ESCC). METHODS: Both LC3 and Pink1 were analyzed by immunohistochemistry in tissues from 217 ESCC patients, including 159 patients undergoing neoadjuvant chemotherapy...
October 11, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29018571/trail-dr5-ctsb-crosstalk-participates-in-breast-cancer-autophagy-initiated-by-saha
#10
Han Han, Hui Zhou, Jing Li, Xiuyan Feng, Dan Zou, Weiqiang Zhou
To investigate the ability of SAHA-induced TRAIL DR5-CTSB crosstalk to initiate the breast cancer autophagy, RTCA assay was performed to assess the effect of SAHA on breast cancer cells, and western blot and ELISA were used to verify the inductive effects on expression of CTSB. Breast cancer cells were transfected with TRAIL DR5 siRNA to block the function of TRAIL DR5. Cell viability and apoptosis of breast cancer cells were analyzed using a muse cell analyzer. The distribution of LC3-II in TRAIL DR5-silenced breast cancer cells treated with SAHA was observed by immunofluorescence microscopy, the mRNA levels of autophagy-related genes were detected by RNA microarray, and the activity of autophagy-related signaling pathways was screened by MAPK antibody array...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29017924/lncrna-cps1-it1-suppresses-emt-and-metastasis-of-colorectal-cancer-by-inhibiting-hypoxia-induced-autophagy-through-inactivation-of-hif-1%C3%AE
#11
Wei Zhang, Weitang Yuan, Junmin Song, Shijun Wang, Xiaoming Gu
OBJECTIVE: Hypoxia is a common phenomenon in solid tumor microenvironment. Thereby, the aim of this study was to investigate the molecular mechanisms of tumor metastasis and epithelial-mesenchymal transition (EMT) regulated by lncRNA CPS1 intronic transcript 1 (CPS1-IT1) under hypoxia in CRC. METHODS: Expression of lncRNA CPS1-IT1, hypoxia-inducible factor-1 alpha (HIF-1α) and autophagy related protein (LC3) were initially assessed in human CRC tissues and in a series of CRC cell lines...
October 7, 2017: Biochimie
https://www.readbyqxmd.com/read/29017913/the-use-of-natural-compounds-for-the-targeting-and-chemoprevention-of-ovarian-cancer
#12
Francesca Pistollato, Ruben Calderón Iglesias, Roberto Ruiz, Silvia Aparicio, Jorge Crespo, Luis Dzul Lopez, Francesca Giampieri, Maurizio Battino
Among gynaecological cancers, ovarian cancer represents the leading cause of death in women. Current treatment for ovarian cancer entails surgery followed by combined chemotherapy with platinum and taxane, which are associated, particularly cisplatin, with severe side effects. While this treatment approach appears to be initially effective in a high number of patients, nearly 70% of them suffer a relapse within a few months after initial treatment. Therefore, more effective and better-tolerated treatment options are clearly needed...
October 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29017179/sgk1-inhibition-induces-autophagy-dependent-apoptosis-via-the-mtor-foxo3a-pathway
#13
Weiwei Liu, Xuchu Wang, Zhenping Liu, Yiyun Wang, Binbin Yin, Pan Yu, Xiuzhi Duan, Zhaoping Liao, Yuhua Chen, Chunhua Liu, Xiang Li, Yibei Dai, Zhihua Tao
BACKGROUND: Although inhibition of SGK1 has been shown to delay cancer progression, the underlying mechanisms have not yet been elucidated. METHODS: We investigated the cellular responses to GSK650394 treatment and SGK1 silencing (or overexpression) in human prostate cancer (PCa) cell lines and PC3 xenografts by flow cytometry, western blotting, immunofluorescence, transmission electron microscopy and immunohistochemistry. RESULTS: In the present study, we demonstrated that SGK1 inhibition, mediated by either GSK650394 or SGK1 shRNA, induced G2/M arrest, apoptosis and autophagy...
October 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28993779/natural-killer-cell-response-to-chemotherapy-stressed-cancer-cells-role-in-tumor-immunosurveillance
#14
REVIEW
Alessandra Zingoni, Cinzia Fionda, Cristiana Borrelli, Marco Cippitelli, Angela Santoni, Alessandra Soriani
Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28991411/structural-insights-into-the-nuclear-import-of-the-histone-acetyltransferase-mof-by-importin-%C3%AE-1
#15
Weili Zheng, Rui Wang, Xi Liu, Siyu Tian, Benqiang Yao, Ang Chen, Shikai Jin, Yong Li
The histone acetyltransferase MOF (males-absent-on-the-first) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences due to the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive...
October 9, 2017: Traffic
https://www.readbyqxmd.com/read/28991259/impaired-p65-degradation-by-decreased-chaperone-mediated-autophagy-activity-facilitates-epithelial-to-mesenchymal-transition
#16
J Tang, M-N Zhan, Q-Q Yin, C-X Zhou, C-L Wang, L-L Wo, M He, G-Q Chen, Q Zhao
Aberrant activation of nuclear factor-κB (NF-κB) has been observed in a wide range of human cancers and is thought to promote tumorigenesis and metastasis. As a central component of NF-κB pathway, p65 protein level is tightly regulated and could be subjected to proteasome degradation. Here we demonstrated that p65 can bind to HSC70 with four consensus recognition motif in its RHD domain and be constitutively transported to the lysosome membrane to bind with lysosome-associated membrane protein type 2A and degraded within the lysosome in two epithelial cell lines, proposing that p65 can be degraded by chaperone-mediated autophagy (CMA)...
October 9, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28990419/proline-metabolism-in-cell-regulation-and-cancer-biology-recent-advances-and-hypotheses
#17
James M Phang
SIGNIFICANCE: It is increasingly clear that proline metabolism plays an important role in metabolic reprogramming, not only in cancer, but also in related fields such as aging, senescence, and development. Although first focused on proline catabolism, recent studies from a number of laboratories have emphasized the regulatory effects of proline synthesis and proline cycling. Recent Advances: Although proline dehydrogenase/proline oxidase (PRODH/POX) has been known as a P53-activated source of redox signaling for initiating apoptosis and autophagy, senescence has been added to the responses...
October 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28990095/kangfuxin-promotes-apoptosis-of-gastric-cancer-cells-through-activating-er%C3%A2-stress-and-autophagy
#18
Pian-Pian Chen, Xiu-Ying Ma, Qian Lin, He-Lin Xu, Hong-Xue Shi, Hong-Yu Zhang, Jian Xiao, Fu-Neng Geng, Ying-Zheng Zhao
Gastric cancer is a leading cause of cancer‑associated mortality worldwide. In studies on the mechanisms of antigastric cancer drugs, autophagy and endoplasmic reticulum (ER) stress have been demonstrated to serve an active role in gastric cancer. The organic extract of Periplaneta americana (also termed American Cockroach), which is named Kangfuxin (KFX) in China, has been used clinically as a traditional Chinese medicine against disorders, including stomach bleeding, gastric ulcers, tuberculosis, burns and trauma...
October 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28989537/effect-of-inhibiting-beclin-1-expression-on-autophagy-proliferation-and-apoptosis-in-colorectal-cancer
#19
Lin Liu, Wei-Min Zhao, Xin-Hui Yang, Zhen-Qiang Sun, Hui-Zhen Jin, Cheng Lei, Bo Jin, Hai-Jiang Wang
The present study aimed to investigate the molecular mechanisms and effect of Beclin-1 on autophagy, proliferation and apoptosis in the colorectal cancer (CRC) HCT116 and SW620 cells. Beclin-1 was silenced by RNA interference (RNAi) in HTC116 and SW620 cells. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of Beclin-1. The percentage of apoptotic cells was analyzed by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Cell cycle and cell proliferation were analyzed by FCM and the MTT assay...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28989041/deciphering-molecular-mechanisms-of-arginine-deiminase-based-therapy-comparative-response-analysis-in-paired-human-primary-and-recurrent-glioblastomas
#20
Claudia Maletzki, Yvonne Rosche, Christin Matzack, Aline Scholz, Doreen William, Carl Friedrich Classen, Bernd Kreikemeyer, Michael Linnebacher, Tomas Fiedler
Arginine auxotrophy constitutes the Achilles' heel for several tumors, among them glioblastoma multiforme (GBM). Hence, arginine-depleting enzymes such as arginine deiminase (ADI) from Streptococcus pyogenes are promising for treatment of primary and maybe even refractory GBM. Based on our previous study in which ADI-susceptibility was shown on a panel of patient-derived GBM cell lines, we here aimed at deciphering underlying molecular mechanisms of ADI-mediated growth inhibition. We found that ADI (35 mU/mL) initially induces a cellular stress-response that is characterized by upregulation of genes primarily belonging to the heat-shock protein family...
October 5, 2017: Chemico-biological Interactions
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