scholarly journals Autophagy and Its Role in Protein Secretion: Implications for Cancer Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Israel Cotzomi-Ortega ◽  
Patricia Aguilar-Alonso ◽  
Julio Reyes-Leyva ◽  
Paola Maycotte
Keyword(s):  
Cancer Therapy ◽  
Cancer Progression ◽  
Protein Secretion ◽  
Survival Function ◽  
Degradation Pathway ◽  
Intercellular Signaling ◽  
Tumor Survival ◽  
Response To Stress ◽  
Secretion Pathways

Autophagy is a protein and organelle degradation pathway important for the maintenance of cytoplasmic homeostasis and for providing nutrients for survival in response to stress conditions. Recently, autophagy has been shown to be important for the secretion of diverse proteins involved in inflammation, intercellular signaling, and cancer progression. The role of autophagy in cancer depends on the stage of tumorigenesis, serving a tumor-suppressor role before transformation and a tumor-survival function once a tumor is established. We review recent evidence demonstrating the complexity of autophagy regulation during cancer, considering the interaction of autophagy with protein secretion pathways. Autophagy manipulation during cancer treatment is likely to affect protein secretion andinter-cellular signaling either to the neighboring cancer cells or to the antitumoral immune response. This will be an important consideration during cancer therapy since several clinical trials are trying to manipulate autophagy in combination with chemotherapy for the treatment of diverse types of cancers.

Cancer Fighting SiRNA-RRM2 Loaded Nanorobots

2020 ◽  
Vol 8 (2) ◽  
pp. 79-90
Author(s):  
Arjun Sharma ◽  
Pravir Kumar ◽  
Rashmi K. Ambasta
Keyword(s):  
Cancer Therapy ◽  
Dna Synthesis ◽  
Cancer Progression ◽  
Sirna Delivery ◽  
Predictive Marker ◽  
The Body ◽  
Tumor Site ◽  
Target Delivery ◽  
Target Effect

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.

scholarly journals Undervalued ubiquitous proteins

4open ◽  
2019 ◽  
Vol 2 ◽  
pp. 7 ◽  
Author(s):  
Björn L.D.M. Brücher ◽  
Ijaz S. Jamall
Keyword(s):  
Cancer Progression ◽  
Cancer Biology ◽  
Life Forms ◽  
Intercellular Signaling ◽  
Peptide Bonds ◽  
True Nature ◽  
The Stability ◽  
Quantitative Contribution ◽  
Ubiquitous Proteins

The role of ubiquitous proteins (UPs) and their corresponding enzymes have been underestimated in carcinogenesis as the focus of much research revolved around measuring mutations and/or other genetic epiphenomena as surrogate markers of cancer and cancer progression. Over the past three decades, the scientific community has come to realize that the concentration on microdissection of cancer cells without accounting for the neighborhood in which these cells reside, i.e., the stroma, fails to reflect the true nature of cancer biology. UPs are fundamental for cellular homeostasis and phylogenetic development as well as for the integrity of the cytoskeleton and for the stability of cells and tissues in regards to intercellular signaling, cell shape and mobility, apoptosis, wound healing, and cell polarity. Corresponding enzymes are used by microorganisms to gain entry into the host by degradation of UPs and play a role to cleave peptide bonds for killing disease-causing life forms along for the creation of the precancerous niche (PCN) during carcinogenesis, cancer invasion, and in metastasis. The language used by such proteins as well as their complementary enzymes with its influence on multiple pathways and the cross-linked extracellular matrix is incompletely understood. The role of UPs in the disruption of signaling homeostasis and resulting interference with crosstalk in carcinogenesis appears sufficiently delineated to warrant a much more refined examination of their qualitative and quantitative contribution to the development of cancer and cancer therapy.

scholarly journals The Hidden Role of Hydrogen Sulfide Metabolism in Cancer

2021 ◽  
Vol 22 (12) ◽  
pp. 6562
Author(s):  
Rong-Hsuan Wang ◽  
Yu-Hsin Chu ◽  
Kai-Ti Lin
Keyword(s):  
Hydrogen Sulfide ◽  
Cancer Therapy ◽  
Cancer Progression ◽  
Cancer Development ◽  
Cancer Types ◽  
Cellular Bioenergetics ◽  
H2s Production ◽  
Anti Inflammation ◽  
Stimulation Of

Hydrogen Sulfide (H2S), an endogenously produced gasotransmitter, is involved in various important physiological and disease conditions, including vasodilation, stimulation of cellular bioenergetics, anti-inflammation, and pro-angiogenesis. In cancer, aberrant up-regulation of H2S-producing enzymes is frequently observed in different cancer types. The recognition that tumor-derived H2S plays various roles during cancer development reveals opportunities to target H2S-mediated signaling pathways in cancer therapy. In this review, we will focus on the mechanism of H2S-mediated protein persulfidation and the detailed information about the dysregulation of H2S-producing enzymes and metabolism in different cancer types. We will also provide an update on mechanisms of H2S-mediated cancer progression and summarize current options to modulate H2S production for cancer therapy.

scholarly journals Structural basis of the differential binding of engineered knottins 2.5F and 2.5D to integrins αVβ3 and α5β1

2019 ◽  
Author(s):  
Johannes F. Van Agthoven ◽  
Hengameh Shams ◽  
Frank V. Cochran ◽  
José L. Alonso ◽  
James R. Kintzing ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Critical Role ◽  
Md Simulations ◽  
Structural Basis ◽  
Conformational Selection ◽  
Drug Candidates ◽  
Tumor Survival ◽  
Differential Binding ◽  
Integrin Ligand

AbstractIntegrins αVβ3 and α5β1 play critical roles in tumor survival, invasion, metastasis, and angiogenesis and are validated targets for cancer therapy and molecular imaging. Increasing evidence suggests that targeting both integrins simultaneously with antagonists is more effective in cancer therapy because of concerns about resistance and paradoxical promotion of tumor growth with use of agents highly selective for a single integrin. Engineered Arg-Gly-Asp (RGD)-containing 3.5 kDa cysteine-knot proteins (knottins 2.5F and 2.5D) are attractive drug candidates due to their exceptional structural stability and high affinity binding to certain integrins. 2.5F binds both αVβ3 and α5β1, whereas 2.5D is αVβ3-selective. To elucidate the structural basis of integrin selection, we determined the structures of 2.5F and 2.5D both as apo-proteins and in complex with αVβ3. These data, combined with MD simulations and mutational studies, revealed a critical role of two αVβ3-specific residues in the vicinity of the metal ion dependent adhesion site (MIDAS) in promoting an αVβ3-induced fit of 2.5D. In contrast, conformational selection accounted for the specificity of 2.5F to both integrins. These data provide new insights into the structural basis of integrin-ligand binding specificity, and could help in development of integrin-targeted therapeutics.

scholarly journals Specialized Pro-Resolving Mediators Mitigate Cancer-Related Inflammation: Role of Tumor-Associated Macrophages and Therapeutic Opportunities

2021 ◽  
Vol 12 ◽  
Author(s):  
Margot Lavy ◽  
Vanessa Gauttier ◽  
Nicolas Poirier ◽  
Sophie Barillé-Nion ◽  
Christophe Blanquart
Keyword(s):  
Cancer Therapy ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Immune Escape ◽  
Therapy Resistance ◽  
High Plasticity ◽  
Tumor Cell Death ◽  
Tumor Associated Macrophages ◽  
Inflammation Resolution

Inflammation is a fundamental physiological response orchestrated by innate immune cells to restore tissue homeostasis. Specialized pro-resolving mediators (SPMs) are involved in active resolution of inflammation but when inflammation is incomplete, chronic inflammation creates a favorable environment that fuels carcinogenesis and cancer progression. Conventional cancer therapy also strengthens cancer-related inflammation by inducing massive tumor cell death that activate surrounding immune-infiltrating cells such as tumor-associated macrophages (TAMs). Macrophages are key actors of both inflammation and its active resolution due to their plastic phenotype. In line with this high plasticity, macrophages can be hijacked by cancer cells to support tumor progression and immune escape, or therapy resistance. Impaired resolution of cancer-associated inflammation supported by TAMs may thus reinforces tumor progression. From this perspective, recent evidence suggests that stimulating macrophage’s pro-resolving functions using SPMs can promote inflammation resolution in cancer and improve anticancer treatments. Thus, TAMs’ re-education toward an antitumor phenotype by using SPMs opens a new line of attack in cancer treatment. Here, we review SPMs’ anticancer capacities with special attention regarding their effects on TAMs. We further discuss how this new therapeutic approach could be envisioned in cancer therapy.

scholarly journals The role of cell adhesion molecule in cancer progression and its application in cancer therapy.

2004 ◽  
Vol 51 (2) ◽  
pp. 445-457 ◽  
Author(s):  
Takatsugu Okegawa ◽  
Rey-Chen Pong ◽  
Yingming Li ◽  
Jer-Tsong Hsieh
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Cancer Therapy ◽  
Adhesion Molecules ◽  
Cancer Progression ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Pivotal Role ◽  
Adhesion Properties

Multiple and diverse cell adhesion molecules take part in intercellular and cell-extracellular matrix interactions of cancer. Cancer progression is a multi-step process in which some adhesion molecules play a pivotal role in the development of recurrent, invasive, and distant metastasis. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of cancer. Loss of intercellular adhesion and the desquamation of cells from the underlying lamina propria allows malignant cells to escape from their site of origin, degrade the extracellular matrix, acquire a more motile and invasion phenotype, and finally, invade and metastasize. In addition to participating in tumor invasiveness and metastasis, adhesion molecules regulate or significantly contribute to a variety of functions including signal transduction, cell growth, differentiation, site-specific gene expression, morphogenesis, immunologic function, cell motility, wound healing, and inflammation. Cell adhesion molecule (CAM), a diverse system of transmembrane glycoproteins has been identified that mediates the cell-cell and cell-extracellular matrix adhesion and also serves as the receptor for different kinds of virus. We summarize recent progress regarding the role of CAM, particularly, immunoglobulin-CAMs and cadherins in the progression of cancer and discuss the potential application of CAMs in the development of cancer therapy mainly on urogenital cancer.

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