Role of ribosomal protein mutations in tumor development (Review)

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

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The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin

International Journal of Molecular Sciences ◽

10.3390/ijms22052250 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2250

Author(s):

Evita Athanasiou ◽

Antonios N. Gargalionis ◽

Fotini Boufidou ◽

Athanassios Tsakris

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Comprehensive Evaluation ◽

Tumor Development ◽

Scientific Data ◽

Malignant Brain Tumor ◽

Direct Role ◽

Tumor Pathology ◽

Human Herpesviruses

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.

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TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Is Upregulated in Lymphocytes Stimulated with Concanavalin A

International Journal of Molecular Sciences ◽

10.3390/ijms22147436 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7436

Author(s):

Helga Simon-Molas ◽

Xavier Vallvé-Martínez ◽

Irene Caldera-Quevedo ◽

Pere Fontova ◽

Claudia Arnedo-Pac ◽

...

Keyword(s):

Concanavalin A ◽

Carbon Flux ◽

Human Lymphocytes ◽

Tumor Development ◽

Pentose Phosphate ◽

Akt Signaling Pathway ◽

G6pdh Activity ◽

Physiological Conditions ◽

Glucose 6 Phosphate Dehydrogenase

The glycolytic modulator TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) is overexpressed in several types of cancer and has a role in metabolic rewiring during tumor development. However, little is known about the role of this enzyme in proliferative tissues under physiological conditions. In the current work, we analysed the role of TIGAR in primary human lymphocytes stimulated with the mitotic agent Concanavalin A (ConA). We found that TIGAR expression was induced in stimulated lymphocytes through the PI3K/AKT pathway, since Akti-1/2 and LY294002 inhibitors prevented the upregulation of TIGAR in response to ConA. In addition, suppression of TIGAR expression by siRNA decreased the levels of the proliferative marker PCNA and increased cellular ROS levels. In this model, TIGAR was found to support the activity of glucose 6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentose phosphate pathway (PPP), since the inhibition of TIGAR reduced G6PDH activity and increased autophagy. In conclusion, we demonstrate here that TIGAR is upregulated in stimulated human lymphocytes through the PI3K/AKT signaling pathway, which contributes to the redirection of the carbon flux to the PPP.

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Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour

International Journal of Molecular Sciences ◽

10.3390/ijms22115560 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5560

Author(s):

Alejandro Álvarez-Artime ◽

Belén García-Soler ◽

Rosa María Sainz ◽

Juan Carlos Mayo

Keyword(s):

Prostate Cancer ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Tumor Development ◽

Cell Types ◽

Protective Role ◽

Bioactive Molecules ◽

Brown Adipose ◽

Endocrine Organs

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.

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The role of heredity in cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.4.527 ◽

1989 ◽

Vol 7 (4) ◽

pp. 527-540 ◽

Cited By ~ 19

Author(s):

E G Levine ◽

R A King ◽

C D Bloomfield

Keyword(s):

Molecular Mechanisms ◽

Familial Cancer ◽

Tumor Development ◽

Future Research ◽

Minor Role ◽

Research Activity ◽

Environmental Interactions ◽

Future Research Directions ◽

A Minor

Heredity is generally felt to play a minor role in the development of cancer. This review critically examines this assumption. Topics discussed include evidence for heritable predisposition in animals and humans; the potential importance of genetic-environmental interactions; approaches that are being used to successfully locate genes responsible for heritable predisposition; comparability of genetic findings among heritable and corresponding sporadic malignancies; and future research directions. Breast, colon, and lung cancer are used to exemplify clinical and research activity in familial cancer; clinical phenotypes, segregation and linkage analyses, models for environmental interactions with inherited traits, and molecular mechanisms of tumor development are discussed. We conclude that the contribution of heredity to the cancer burden is greater than generally accepted, and that study of heritable predisposition will continue to reveal carcinogenic mechanisms important to the development of all cancers.

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Investigating New Therapeutic Strategies Targeting Hyperinsulinemia's Mitogenic Effects in a Female Mouse Breast Cancer Model

Endocrinology ◽

10.1210/en.2012-2263 ◽

2013 ◽

Vol 154 (5) ◽

pp. 1701-1710 ◽

Cited By ~ 21

Author(s):

Ran Rostoker ◽

Keren Bitton-Worms ◽

Avishay Caspi ◽

Zila Shen-Orr ◽

Derek LeRoith

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Breast Tumor ◽

Experimental Studies ◽

Tumor Development ◽

Treated Group ◽

Tumor Growth Rate ◽

Breast Cancer Patients ◽

Mitogenic Effect

Abstract Epidemiological and experimental studies have identified hyperinsulinemia as an important risk factor for breast cancer induction and for the poor prognosis in breast cancer patients with obesity and type 2 diabetes. Recently it was demonstrated that both the insulin receptor (IR) and the IGF-IR mediate hyperinsulinemia's mitogenic effect in several breast cancer models. Although IGF-IR has been intensively investigated, and anti-IGF-IR therapies are now in advanced clinical trials, the role of the IR in mediating hyperinsulinemia's mitogenic effect remains to be clarified. Here we aimed to explore the potential of IR inhibition compared to dual IR/IGF-IR blockade on breast tumor growth. To initiate breast tumors, we inoculated the mammary carcinoma Mvt-1 cell line into the inguinal mammary fat pad of the hyperinsulinemic MKR female mice, and to study the role of IR, we treated the mice bearing tumors with the recently reported high-affinity IR antagonist-S961, in addition to the well-documented IGF-IR inhibitor picropodophyllin (PPP). Although reducing IR activation, with resultant severe hyperglycemia and hyperinsulinemia, S961-treated mice had significantly larger tumors compared to the vehicle-treated group. This effect maybe secondary to the severe hyperinsulinemia mediated via the IGF-1 receptor. In contrast, PPP by partially inhibiting both IR and IGF-IR activity reduced tumor growth rate with only mild metabolic consequences. We conclude that targeting (even partially) both IR and IGF-IRs impairs hyperinsulinemia's effects in breast tumor development while simultaneously sparing the metabolic abnormalities observed when targeting IR alone with virtual complete inhibition.

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