miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer

e23175 Background: PD-1/PD-L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy for certain non-small cell lung cancer (NSCLC) patients. Methods: PD-L1 and E6 oncoprotein expressions in lung tumors from 122 NSCLC patients were examined by immunohistochemistry and their prognostic value was evaluated by Kaplain-Meier and Cox regression analysis. HPV16-postive and negative TL-1 and TL-4 lung cancer and SiHa and C33A cervical cancer cells were used to test whether PD-L1 expression could be regulated by E6, not by E7 oncoprotein. Immune deficiency nude mice were used to test the possibility that combining anti-PD-L1 mAb with Lm-LLO-E6 vaccine could have a higher antitumor activity compared with anti-PD-L1 mAb or Lm-LLO-E6 vaccine alone. Results: Immunohistochemistry analysis indicated that PD-L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD-L1-positive/E6-positive tumor. PD-L1 expression was increased by the expression of E6, but not the E7, oncoprotein in lung and cervical cancer cells. PD-L1 expression was responsible for E6-mediated colony formation and soft agar growth. Therefore, PD-L1 secreted from tumor cells may directly promote tumor progression, particularly in E6-positive tumors. A greater antitumor activity was obtained with anti-PD-L1 mAb+Lm-LLO-E6 vaccine than with anti-PD-L1 mAb or Lm-LLO-E6 alone in subcutaneous and metastatic tumors induced by TL-1 and SiHa cells. The longest survival time for nude mice was observed in the anti-PD-L1 mAb+Lm-LLO-E6 vaccine group. Conclusions: An anti-PD-L1 mAb+Lm-LLO-E6 vaccine may be an efficient treatment for suppression of tumor growth and metastasis induced by HPV-infected cells.

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Systemic Platelet-activating Factor Receptor Activation Augments Experimental Lung Tumor Growth and Metastasis

Cancer Growth and Metastasis ◽

10.4137/cgm.s14501 ◽

2014 ◽

Vol 7 ◽

pp. CGM.S14501 ◽

Cited By ~ 15

Author(s):

Patrick C. Hackler ◽

Sarah Reuss ◽

Raymond L. Konger ◽

Jeffrey B. Travers ◽

Ravi P. Sahu

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Cancer Progression ◽

Lung Tumor ◽

Platelet Activating Factor ◽

Receptor Activation ◽

Dependent Manner ◽

Melanoma Tumor ◽

Tumor Growth And Metastasis ◽

The Impact

Pro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we demonstrate that treatment of C57BL/6 mice with a PAF-R agonist augments tumor growth and lung metastasis in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was because of host rather than tumor cells PAF-R dependent as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.

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Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis

Cell Death and Disease ◽

10.1038/s41419-021-04193-7 ◽

2021 ◽

Vol 12 (10) ◽

Author(s):

Chunyu Zhang ◽

Pan Liu ◽

Jiaming Huang ◽

Yuandong Liao ◽

Chaoyun Pan ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Poor Prognosis ◽

Prognostic Biomarker ◽

Circular Rna ◽

Circular Rnas ◽

Inhibit Tumor Growth ◽

Cancer Tumor ◽

Tumor Growth And Metastasis

AbstractCircular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.

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RNA-seq reveals novel mechanistic targets of withaferin A in prostate cancer cells

Carcinogenesis ◽

10.1093/carcin/bgaa009 ◽

2020 ◽

Vol 41 (6) ◽

pp. 778-789 ◽

Cited By ~ 5

Author(s):

Su-Hyeong Kim ◽

Eun-Ryeong Hahm ◽

Krishna B Singh ◽

Sruti Shiva ◽

Jacob Stewart-Ornstein ◽

...

Keyword(s):

Prostate Cancer ◽

Fatty Acid ◽

Fatty Acid Synthase ◽

Acid Synthesis ◽

Acetyl Coa Carboxylase ◽

Rna Seq ◽

Atp Citrate Lyase ◽

Acetyl Coa ◽

Citrate Lyase

Abstract Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activities against prostate and other cancers, but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A. Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of acetyl-CoA carboxylase 1 and fatty acid synthase protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A proteins in the prostate in vivo.

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RETRACTED ARTICLE: Decreased Warburg effect induced by ATP citrate lyase suppression inhibits tumor growth in pancreatic cancer

Medical Oncology ◽

10.1007/s12032-015-0540-z ◽

2015 ◽

Vol 32 (3) ◽

Cited By ~ 6

Author(s):

Haifeng Zong ◽

Yang Zhang ◽

Yong You ◽

Tiantian Cai ◽

Yehuang Wang

Keyword(s):

Pancreatic Cancer ◽

Tumor Growth ◽

Warburg Effect ◽

Atp Citrate Lyase ◽

Citrate Lyase ◽

Retracted Article

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Correction: Inhibition of Invasion, Angiogenesis, Tumor Growth, and Metastasis by Adenovirus-Mediated Transfer of Antisense uPAR and MMP-9 in Non–Small Cell Lung Cancer Cells

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-13-0887 ◽

2013 ◽

Vol 12 (12) ◽

pp. 2963-2964

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Small Cell ◽

Lung Cancer Cells ◽

Small Cell Lung ◽

Tumor Growth And Metastasis

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Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis

Cancer Research ◽

10.1158/0008-5472.can-14-3297 ◽

2015 ◽

Vol 75 (14) ◽

pp. 2949-2960 ◽

Cited By ~ 47

Author(s):

Chun-Jung Ko ◽

Cheng-Chung Huang ◽

Hsin-Ying Lin ◽

Chun-Pai Juan ◽

Shao-Wei Lan ◽

...

Keyword(s):

Prostate Cancer ◽

Extracellular Matrix ◽

Tumor Growth ◽

Cancer Cell ◽

Cell Invasion ◽

Prostate Cancer Cell ◽

Matrix Degradation ◽

Cancer Cell Invasion ◽

Extracellular Matrix Degradation ◽

Tumor Growth And Metastasis

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Prognostic Value of Malic Enzyme and ATP-Citrate Lyase in Non-Small Cell Lung Cancer of the Young and the Elderly

PLoS ONE ◽

10.1371/journal.pone.0126357 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0126357 ◽

Cited By ~ 16

Author(s):

Agnes Csanadi ◽

Claudia Kayser ◽

Marcel Donauer ◽

Vera Gumpp ◽

Konrad Aumann ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Malic Enzyme ◽

Prognostic Value ◽

The Elderly ◽

Small Cell ◽

Small Cell Lung ◽

Atp Citrate Lyase ◽

Citrate Lyase

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Bradykinin-related compounds as new drugs for cancer and inflammation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y02-030 ◽

2002 ◽

Vol 80 (4) ◽

pp. 275-280 ◽

Cited By ~ 30

Author(s):

John M Stewart ◽

Lajos Gera ◽

Daniel C Chan ◽

Paul A Bunn Jr. ◽

Eunice J York ◽

...

Keyword(s):

Prostate Cancer ◽

Lung Cancer ◽

Tumor Growth ◽

Small Cell Lung Cancer ◽

Nude Mice ◽

Small Cell ◽

Small Cell Lung ◽

Related Compounds

Bradykinin (BK) (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an important growth factor for small-cell lung cancer (SCLC) and prostate cancer (PC). These cancers have cells of neuroendocrine origin and express receptors for a variety of neuropeptides. BK receptors are expressed on almost all lung cancer cell lines and on many PC cells. Our very potent BK antagonist B9430 (D-Arg-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic-Arg) (Hyp, trans-4-hydroxy-L-proline; Igl, α-2-indanylglycine; Oic, octahydroindole-2-carboxylic acid) is a candidate anti-inflammatory drug but does not inhibit growth of SCLC or PC. When B9430 is dimerized by N-terminal cross-linking with a suberimide linker, the product B9870 is a potent growth inhibitor for SCLC both in vitro and in vivo in athymic nude mice. Daily i.p. injection at 5 mg·kg1·day1 beginning on day 8 after SCLC SHP-77 cell implantation gave 65% inhibition of tumor growth. B9870 stimulates apoptosis in SCLC by a novel "biased agonist" action. We have also developed new small mimetic antagonists. BKM-570 (F5C-OC2Y-Atmp) (F5C, pentafluorocinnamic acid; OC2Y, O-2,6-dichlorobenzyl tyrosine; Atmp, 4-amino-2,2,6,6-tetramethylpiperidine) is very potent for inhibition of SHP-77 growth in nude mice. When injected daily i.p. at 5 mg·kg1, M-570 gave 90% suppression of tumor growth. M-570 is more potent than the well-known anticancer drug cisPlatin (60% inhibition) or the recently developed SU5416 (40% inhibition) in this model. M-570 also showed activity against various other cancer cell lines in vitro (SCLC, non-SCLC, lung, prostate, colon, cervix) and inhibited growth of prostate cell line PC3 in nude mice. M-570 and related compounds evidently act in vivo through pathways other than BK receptors. These compounds have clinical potential for treatment of human lung and prostate cancers.Key words: bradykinin antagonists, cancer, inflammation, prostate cancer, small cell lung cancer.

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