scholarly journals Current Structural Knowledge on the CNNM Family of Magnesium Transport Mediators

2019 ◽  
Vol 20 (5) ◽  
pp. 1135 ◽  
Author(s):  
Paula Giménez-Mascarell ◽  
Irene González-Recio ◽  
Cármen Fernández-Rodríguez ◽  
Iker Oyenarte ◽  
Dominik Müller ◽  
...  
Keyword(s):  
Structural Knowledge ◽  
Co2 Efflux ◽  
Magnesium Transport ◽  
Cbs Domain ◽  
Promote Tumor Growth ◽  
Exact Function ◽  
Familial Hypomagnesemia ◽  
Altered Blood ◽  
Tumor Growth And Metastasis ◽  
Human Family

The cyclin and cystathionine β-synthase (CBS) domain magnesium transport mediators, CNNMs, are key players in maintaining the homeostasis of magnesium in different organs. The human family includes four members, whose impaired activity causes diseases such as Jalili Syndrome or Familial Hypomagnesemia, but is also linked to neuropathologic disorders, altered blood pressure, and infertility. Recent findings demonstrated that CNNMs are associated with the highly oncogenic phosphatases of the regenerating liver to promote tumor growth and metastasis, which has attracted renewed focus on their potential exploitation as targets for cancer treatment. However, the exact function of CNNMs remains unclear and is subject to debate, proposed as either direct transporters, sensors, or homeostatic factors. This review gathers the current structural knowledge on the CNNM family, highlighting similarities and differences with the closely related structural partners such as the bacterial Mg2+/Co2+ efflux protein CorC and the Mg2+ channel MgtE.

scholarly journals IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Kewei Liu ◽  
Ai Huang ◽  
Jun Nie ◽  
Jun Tan ◽  
Shijie Xing ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Immune Cells ◽  
Immune Checkpoint Blockade ◽  
Future Research ◽  
Barr Virus ◽  
Promote Tumor Growth ◽  
Epstein Barr ◽  
Mechanistic Basis ◽  
Tumor Growth And Metastasis

Interleukin-35 (IL-35) is a heterodimeric cytokine composed of Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35 that has recently been shown to play diverse and important roles in the tumor microenvironment (TME). Owing to its immunosuppressive activity and ability to promote tumor growth and progression, IL-35 is widely recognized as a key mediator of TME status. Immune cells are key mediators of diverse tumor-related phenotypes, and immunosuppressive cytokines such as IL-35 can promote tumor growth and metastasis in TME. These influences should be considered together. Since tumor immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance, a new target or efficacy enhancing factor is urgently needed. Suppressing IL-35 production and activity has been demonstrated as an effective factor that inhibits tumor cells viability, and further investigation of this cytokine is warranted. However, the mechanistic basis for IL-35-mediated regulation of immune cells in the TME remains to be fully clarified. In the present review, we explore the roles of IL-35 in regulating immune cells within the TME. In addition, we highlight IL-35 as a specific immunological target and discuss its possible relevance in the context of immunotherapy. Lastly, we sought to summarize potential future research directions that may guide the advancement of current understanding regarding the role of this important cytokine as a regulator of oncogenesis.

scholarly journals WNK1 Kinase Stimulates Angiogenesis to Promote Tumor Growth and Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 575 ◽  
Author(s):  
Zong-Lin Sie ◽  
Ruei-Yang Li ◽  
Bonifasius Putera Sampurna ◽  
Po-Jui Hsu ◽  
Shu-Chen Liu ◽  
...  
Keyword(s):  
Hepatoma Cells ◽  
Transgenic Zebrafish ◽  
Human Hepatoma Cells ◽  
Vessel Formation ◽  
Vegf Signaling ◽  
Promote Tumor Growth ◽  
Chemical Inhibitors ◽  
Wnk Kinases ◽  
Tumor Growth And Metastasis ◽  
Endothelial Growth Factor

With-no-lysine (K)-1 (WNK1) is the founding member of family of four protein kinases with atypical placement of catalytic lysine that play important roles in regulating epithelial ion transport. Gain-of-function mutations of WNK1 and WNK4 cause a mendelian hypertension and hyperkalemic disease. WNK1 is ubiquitously expressed and essential for embryonic angiogenesis in mice. Increasing evidence indicates the role of WNK kinases in tumorigenesis at least partly by stimulating tumor cell proliferation. Here, we show that human hepatoma cells xenotransplanted into zebrafish produced high levels of vascular endothelial growth factor (VEGF) and WNK1, and induced expression of zebrafish wnk1. Knockdown of wnk1 in zebrafish decreased tumor-induced ectopic vessel formation and inhibited tumor proliferation. Inhibition of WNK1 or its downstream kinases OSR1 (oxidative stress responsive kinase 1)/SPAK (Ste20-related proline alanine rich kinase) using chemical inhibitors decreased ectopic vessel formation as well as proliferation of xenotransplanted hepatoma cells. The effect of WNK and OSR1 inhibitors is greater than that achieved by inhibitor of VEGF signaling cascade. These inhibitors also effectively inhibited tumorigenesis in two separate transgenic zebrafish models of intestinal and hepatocellular carcinomas. Endothelial-specific overexpression of wnk1 enhanced tumorigenesis in transgenic carcinogenic fish, supporting endothelial cell-autonomous effect of WNK1 in tumor promotion. Thus, WNK1 can promote tumorigenesis by multiple effects that include stimulating tumor angiogenesis. Inhibition of WNK1 may be a potent anti-cancer therapy.

scholarly journals Low Doses of Ionizing Radiation Promote Tumor Growth and Metastasis by Enhancing Angiogenesis

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e11222 ◽  
Author(s):  
Inês Sofia Vala ◽  
Leila R. Martins ◽  
Natsuko Imaizumi ◽  
Raquel J. Nunes ◽  
José Rino ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Tumor Growth ◽  
Low Doses ◽  
Promote Tumor Growth ◽  
Tumor Growth And Metastasis

Tumor-Associated Macrophages as Potential Targets for Anti-Cancer Activity of Marine Invertebrate-Derived Compounds

2021 ◽  
Vol 27 ◽  
Author(s):  
Lyudmila S. Dolmatova ◽  
Igor Yu. Dolmatov
Keyword(s):  
Marine Invertebrates ◽  
Marine Invertebrate ◽  
Mechanisms Of Action ◽  
Tumor Associated Macrophages ◽  
Drug Candidates ◽  
Promote Tumor Growth ◽  
Anti Cancer ◽  
M1 Phenotype ◽  
Marine Compounds ◽  
Tumor Growth And Metastasis

: Tumor-associated macrophages (TAMs) are M2 phenotype dominant and promote tumor growth and metastasis. The new cancer treatment strategy includes TAM targeting and is aimed primarily at reprogramming TAMs toward the M1 phenotype or reducing the number and activity of M2 macrophages. Several marine invertebrate-derived drugs, combining efficacy and a low level of side effects, were approved for use in the cancer therapy. The mechanisms of action of some of them include TAM targeting. The review includes data showing immunomodulatory properties of these already approved anticancer drugs and drug candidates in clinical development which additionally incorporate data from screening studies of new substances from marine invertebrates. Based on screening data, the most promising marine compounds for cancer immunotherapy are supposed.

scholarly journals Assessment of the Effect of Sorafenib on Omega-6 and Omega-3 Epoxyeicosanoid Formation in Patients with Hepatocellular Carcinoma

2020 ◽  
Vol 21 (5) ◽  
pp. 1875 ◽  
Author(s):  
Can G. Leineweber ◽  
Anne Pietzner ◽  
Ingrid W. Zhang ◽  
Usha B. Blessin ◽  
Michael Rothe ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Experimental Studies ◽  
Small Sample ◽  
Omega 3 ◽  
Multikinase Inhibitor ◽  
Sorafenib Treatment ◽  
Promote Tumor Growth ◽  
Omega 6 ◽  
Tumor Growth And Metastasis ◽  
Anti Tumor Activity

Hepatocellular carcinoma (HCC) is a leading cause of cancer death. The multikinase inhibitor sorafenib is widely used for systemic therapy in advanced HCC. Sorafenib might affect epoxyeicosanoids, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of epoxides derived from long-chain polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding diols. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) showed that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this pilot study, we assessed the effect of sorafenib treatment on the presence of lipid mediators, such as EETs, in blood of the patients with HCC using the lipidomics technology. We found a significant increase in 11,12-EET and 14,15-EET levels in HCC patients treated with sorafenib. Furthermore, while not significant in this small sample set, the data presented indicate that sorafenib can also increase the level of omega-3 DHA-derived 19,20-EDP. While the effect on EETs might hamper the anti-tumor effect of sorafenib, we hypothesize that supplementation of DHA in sorafenib-treated HCC patients could increase the level of 19,20-EDP and thereby enhance its anti-tumor effect.

Clinicopathological Significance of HO-1 and HO-2 Expression in Medulloblastoma

2014 ◽  
Vol 881-883 ◽  
pp. 469-472
Author(s):  
Li Tang ◽  
Li Yu
Keyword(s):  
Brain Tumors ◽  
Tumor Growth ◽  
Pediatric Brain Tumors ◽  
Potential Therapeutic Target ◽  
Intracellular Enzyme ◽  
Promote Tumor Growth ◽  
Clinicopathological Significance ◽  
Tumor Growth And Metastasis ◽  
Rate Limiting ◽  
Pediatric Brain

Heme oxygenase (HO) is the rate-limiting intracellular enzyme of heme catabolism. Overexpressed HO-1 can inhibit the apoptosis of tumor cells and promote tumor growth and metastasis, and (HO-1) has been considereded to play a major role in the pathogenesis of many tumors. Medulloblastomas (MB) are the most common malignant brain tumors in children and constitute 20% of all pediatric brain tumors. However, there is no report about clinicopathological significance of HO-1 and HO-2 expression in medulloblastoma (MB). In the present study, to explore the expression and potential function of HO in MBs, immunohistochemistry was used to examine the HO-1 and HO-2 expression in 41 MBs. The result showed that immunoreactivity of HO-1 was detected in 32 of 41 MBs and HO-2 was detected in 30 of 41 MBs, and their expression level had no significant correlations with the clinical features of the patients and subtypes of MB. In addition, the prognoses were better in those high HO-1 expression and low HO-2 expression cases. Taken together, the expression of HO-1 and HO-2 protein is significantly correlated with tumor growth in MB. The co-ordinated expression of HO-1 and HO-2 may affect the survival of MB patients. These results suggest that HO-1 may be a potential therapeutic target for MB.

scholarly journals DOPAMINERGIC SYSTEM: STRESS, DEPRESSION AND CANCER (PART 2)

2019 ◽  
Vol 18 (4) ◽  
pp. 25-33
Author(s):  
O. A. Bocharova ◽  
E. V. Bocharov ◽  
V. G. Kucheryanu ◽  
R. V. Karpova ◽  
A. A. Vershinskaya
Keyword(s):  
Dopaminergic System ◽  
Acute Stress ◽  
Growth Control ◽  
The Body ◽  
Age Related ◽  
Promote Tumor Growth ◽  
Neuronal Processes ◽  
Tumor Growth And Metastasis ◽  
Positive Effect

In today’s world, we are constantly exposed to stress. At the same time, if acute stress can have a positive effect on the body, constant stress usually harms health, leading to serious diseases, including cancer, which is considered to be age-related disease. It is also known that stress can significantly deteriorate the efficacy of chemotherapies and anti-tumour immune response, promote tumor growth and metastasis spreading. Meanwhile dopamin known to be antiaging and antistress agent is able to inhibit tumourgenesis. Therefore the role of Central neuronal processes involving the dopaminergic system in the mechanisms of malignant growth control is discussed in the present review.

scholarly journals GRHL3 Promotes Tumor Growth and Metastasis via the MEK Pathway in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lin Tan ◽  
Weiming Qu ◽  
Dajun Wu ◽  
Minji Liu ◽  
Qian Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Underlying Mechanism ◽  
Promoting Effect ◽  
Promote Tumor Growth ◽  
Proliferation And Metastasis ◽  
Tumor Growth And Metastasis ◽  
Cell Proliferation And Metastasis

GRHL3 is a factor associated with a tumor, of which the molecular mechanism remains a further investigation. We explored the underlying mechanism of tumor-promoting effect of GRHL3 in colorectal cancer (CRC), which is involved in the MEK1/2 pathway. The expression of GRHL3 was measured in CRC and adjacent normal tissue using qPCR and immunohistochemical staining. Lentivirus-mediated knockdown expression of GRHL3 was performed in the CRC cell line HT29. Cell proliferation and metastasis were assayed in vitro, and tumorigenicity was investigated in vivo. We found higher GRHL3 expression in colorectal cancer, which was negatively correlated with patients’ prognosis. Results from studies in vitro and in vivo indicated that downregulation of GRHL3 expression inhibited tumor growth and metastasis and inhibited the activation of the MEK1/2 pathway. The effect of GRHL3 downexpression was the same as that of MEK1/2 antagonists on suppression of tumor growth and metastasis. Our results suggested that GRHL3 may act as an oncogene to promote tumor growth and metastasis via the MEK pathway in colorectal cancer.

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