scholarly journals The Role of Cysteine Cathepsins in Cancer Progression and Drug Resistance

2019 ◽  
Vol 20 (14) ◽  
pp. 3602 ◽  
Author(s):  
Magdalena Rudzińska ◽  
Alessandro Parodi ◽  
Surinder M. Soond ◽  
Andrey Z. Vinarov ◽  
Dmitry O. Korolev ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Lysosomal Enzymes ◽  
Tumor Biology ◽  
Therapeutic Strategies ◽  
Cysteine Cathepsins ◽  
Aggressive Tumor ◽  
Tumor Phenotypes

Cysteine cathepsins are lysosomal enzymes belonging to the papain family. Their expression is misregulated in a wide variety of tumors, and ample data prove their involvement in cancer progression, angiogenesis, metastasis, and in the occurrence of drug resistance. However, while their overexpression is usually associated with highly aggressive tumor phenotypes, their mechanistic role in cancer progression is still to be determined to develop new therapeutic strategies. In this review, we highlight the literature related to the role of the cysteine cathepsins in cancer biology, with particular emphasis on their input into tumor biology.

The Role of Cancer-associated Fibroblasts in Tumorigenesis of Gastric Cancer

2018 ◽  
Vol 24 (28) ◽  
pp. 3297-3302 ◽  
Author(s):  
Zhilong Ma ◽  
Min Chen ◽  
Xiaohu Yang ◽  
Bin Xu ◽  
Zhenshun Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Biology ◽  
Vital Role ◽  
Cancer Associated Fibroblasts ◽  
Gastric Cancer Cells ◽  
Stromal Fibroblasts ◽  
Tumor Microenvironments ◽  
Tumorigenesis And Progression

Cancer-associated fibroblasts (CAFs) are an important cell type present in solid tumor microenvironments, including that of gastric cancer. They play a vital role in the promotion of tumorigenesis, angiogenesis, and cancer progression through paracrine signaling and modulation of the extracellular matrix. However, the exact molecular mechanism underlying the interaction between gastric cancer cells and stromal fibroblasts remains poorly understood. Recent studies have demonstrated that various factors, such as gene and microRNA variations, are involved in this process. This review discusses recent advances in understanding how these factors are regulated in CAFs and how they affect tumor biology, which may improve our understanding of their role in gastric cancer tumorigenesis and progression and provide new promising targets for therapeutic strategies.

scholarly journals Multifaceted role of tensins in cancer

2019 ◽  
Author(s):  
Abdulaziz Alfahed ◽  
Teresa P Raposo ◽  
Mohammad Ilyas
Keyword(s):  
Cancer Biology ◽  
Focal Adhesions ◽  
Adaptor Proteins ◽  
Therapeutic Strategies ◽  
Cell Behavior ◽  
Surrounding Environment ◽  
Signaling Mechanisms ◽  
Different Types ◽  
Biochemical Signals

Tensins are structural adaptor proteins localized at focal adhesions. Tensins can act as mechanosensors and participate in the transduction of biochemical signals from the extracellular matrix to the cytoskeleton, acting as an interface able to alter cell behavior in responses to changes in their surrounding environment. This review aims to provide a concise summary of the main functions of the four known tensins in cell and cancer biology, their homology and recently unveiled signaling mechanisms. We focus specifically on how tensin 4 (TNS4/Cten) may contribute to cancer both as an oncogene supporting metastasis and as tumour suppressor in different types of tissue. A better understanding of the cancer mechanistics involving tensins may provide the rationale for development of specific therapeutic strategies.

The role of microvesicles in cancer progression and drug resistance

2013 ◽  
Vol 41 (1) ◽  
pp. 293-298 ◽  
Author(s):  
Samireh Jorfi ◽  
Jameel M. Inal
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Progression ◽  
Chemotherapeutic Agents ◽  
Malignant Cells ◽  
Intercellular Transport ◽  
Wide Range ◽  
Anti Cancer ◽  
Mdr Multidrug Resistance

Microvesicles are shed constitutively, or upon activation, from both normal and malignant cells. The process is dependent on an increase in cytosolic Ca2+, which activates different enzymes, resulting in depolymerization of the actin cytoskeleton and release of the vesicles. Drug resistance can be defined as the ability of cancer cells to survive exposure to a wide range of anti-cancer drugs, and anti-tumour chemotherapeutic treatments are often impaired by innate or acquired MDR (multidrug resistance). Microvesicles released upon chemotherapeutic agents prevent the drugs from reaching their targets and also mediate intercellular transport of MDR proteins.

scholarly journals Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors

2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Tumor Development ◽  
Short Paper ◽  
Great Relevance ◽  
Cellular Components ◽  
The Relationship

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

scholarly journals Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 396
Author(s):  
Estíbaliz Tamayo-Orbegozo ◽  
Laura Amo ◽  
Javier Díez-García ◽  
Elena Amutio ◽  
Marta Riñón ◽  
...  
Keyword(s):  
Drug Resistance ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Cell Types ◽  
Metabolic Reprogramming ◽  
Non Hodgkin Lymphoma ◽  
New Evidence

Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.

scholarly journals Acquired Resistance to Clinical Cancer Therapy: A Twist in Physiological Signaling

2016 ◽  
Vol 96 (3) ◽  
pp. 805-829 ◽  
Author(s):  
Andreas Wicki ◽  
Mario Mandalà ◽  
Daniela Massi ◽  
Daniela Taverna ◽  
Huifang Tang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Immune System ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Therapeutic Strategies ◽  
Host Immune System ◽  
Cancer Therapies ◽  
Acquired Drug Resistance ◽  
Physiological Signal

Although modern therapeutic strategies have brought significant progress to cancer care in the last 30 years, drug resistance to targeted monotherapies has emerged as a major challenge. Aberrant regulation of multiple physiological signaling pathways indispensable for developmental and metabolic homeostasis, such as hyperactivation of pro-survival signaling axes, loss of suppressive regulations, and impaired functionalities of the immune system, have been extensively investigated aiming to understand the diversity of molecular mechanisms that underlie cancer development and progression. In this review, we intend to discuss the molecular mechanisms of how conventional physiological signal transduction confers to acquired drug resistance in cancer patients. We will particularly focus on protooncogenic receptor kinase inhibition-elicited tumor cell adaptation through two major core downstream signaling cascades, the PI3K/Akt and MAPK pathways. These pathways are crucial for cell growth and differentiation and are frequently hyperactivated during tumorigenesis. In addition, we also emphasize the emerging roles of the deregulated host immune system that may actively promote cancer progression and attenuate immunosurveillance in cancer therapies. Understanding these mechanisms may help to develop more effective therapeutic strategies that are able to keep the tumor in check and even possibly turn cancer into a chronic disease.

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.

Sign in / Sign up

Export Citation Format

Share Document