scholarly journals Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Zihe Guo ◽  
Ayao Guo ◽  
Chuang Zhou
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Treatment Strategies ◽  
Dependent Manner ◽  
Promote Cell Migration ◽  
Cancer Aggressiveness ◽  
Novel Treatment Strategies ◽  
Underlying Mechanisms

Continuous chemotherapy pressure-elicited annexin-A6 (ANXA6)-containing exosome (ANXA6-exo) secretion contributes to paclitaxel (PTX) resistance in breast cancer (BC), but the molecular mechanisms are not fully elucidated. The present study managed to investigate this issue and found that ANXA6-exo promoted PTX resistance and cancer progression in BC cells in a Yes-associated protein 1 (YAP1)-dependent manner. Specifically, the parental PTX-sensitive BC (PS-BC) cells were exposed to continuous low-dose PTX to generate PTX-resistant BC (PR-BC) cells, and we found that BC stem cells tended to be enriched in the descendent PR-BC cells in contrast with the PS-BC cells. In addition, PR-BC cell-derived exosomes were featured with highly expressed ANXA6, and ANXA6-exo delivered ANXA6 to promote cell migration, growth, autophagy, and stemness in PS-BC cells. Interestingly, ANXA6-exo increased PTX resistance in PS-BC cells via inducing autophagy, and the effects of ANXA6-exo on PTX resistance in PS-BC cells were abrogated by co-treating cells with the autophagy inhibitor 3-methyladenine. Moreover, the underlying mechanisms were uncovered, and we evidenced that ANXA6-exo up-regulated YAP1 to promote Hippo pathway dysregulation, and the promoting effects of ANXA6-exo on PTX resistance and cancer aggressiveness in BC cells were abrogated by silencing YAP1. Taken together, this study firstly elucidated the underlying mechanisms by which BCSC-derived ANXA6-exo facilitated BC progression and PTX resistance, which might help to develop novel treatment strategies for BC in clinic.

scholarly journals Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chongru Zhao ◽  
Weijie Hu ◽  
Yi Xu ◽  
Dawei Wang ◽  
Yichen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Energy Homeostasis ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Novel Treatment ◽  
Common Cancer ◽  
Prevalence Of Obesity ◽  
Novel Treatment Strategies ◽  
Underlying Mechanisms ◽  
The Impact

Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.

scholarly journals Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC

2021 ◽  
Author(s):  
Andrew Sulaiman ◽  
Sarah McGarry ◽  
Sai Charan Chilumula ◽  
Vishak Vinod ◽  
Rohith Kandunuri
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Treatment Strategies ◽  
Major Barrier ◽  
Differential Signal ◽  
Growth Factor Beta ◽  
Novel Treatment Strategies ◽  
Patient Prognosis

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44+/CD24-) and epithelial (ALDHhigh) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

scholarly journals Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1386
Author(s):  
Andrew Sulaiman ◽  
Sarah McGarry ◽  
Sai Charan Chilumula ◽  
Rohith Kandunuri ◽  
Vishak Vinod
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Treatment Strategies ◽  
Major Barrier ◽  
Differential Signal ◽  
Growth Factor Beta ◽  
Novel Treatment Strategies ◽  
Patient Prognosis

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC, which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44+/CD24−) and epithelial (ALDHhigh) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation, which may lead to the development of novel therapies to improve TNBC patient prognosis.

scholarly journals KIF14 negatively regulates Rap1a–Radil signaling during breast cancer progression

2012 ◽  
Vol 199 (6) ◽  
pp. 951-967 ◽  
Author(s):  
Syed M. Ahmed ◽  
Brigitte L. Thériault ◽  
Maruti Uppalapati ◽  
Catherine W.N. Chiu ◽  
Brenda L. Gallie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Pdz Domain ◽  
Cell Spreading ◽  
Small Gtpase ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Integrin Activation ◽  
Inside Out

The small GTPase Rap1 regulates inside-out integrin activation and thereby influences cell adhesion, migration, and polarity. Several Rap1 effectors have been described to mediate the cellular effects of Rap1 in a context-dependent manner. Radil is emerging as an important Rap effector implicated in cell spreading and migration, but the molecular mechanisms underlying its functions are unclear. We report here that the kinesin KIF14 associates with the PDZ domain of Radil and negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. The depletion of KIF14 led to increased cell spreading, altered focal adhesion dynamics, and inhibition of cell migration and invasion. We also show that Radil is important for breast cancer cell proliferation and for metastasis in mice. Our findings provide evidence that the concurrent up-regulation of Rap1 activity and increased KIF14 levels in several cancers is needed to reach optimal levels of Rap1–Radil signaling, integrin activation, and cell–matrix adhesiveness required for tumor progression.

Regulation of Breast Cancer Progression by Noncoding RNAs

2020 ◽  
Vol 20 (10) ◽  
pp. 757-767
Author(s):  
Ravishkumar L. Akshaya ◽  
Muthukumar Rohini ◽  
Nagarajan Selvamurugan
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Tumor Suppressors ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Breast Carcinogenesis ◽  
Small Ncrnas ◽  
Underlying Mechanisms ◽  
Cycle Regulation ◽  
Crucial Part

Background: Breast cancer (BC) is the cardinal cause of cancer-related deaths among women across the globe. Our understanding of the molecular mechanisms underlying BC invasion and metastasis remains insufficient. Recent studies provide compelling evidence on the prospective contribution of noncoding RNAs (ncRNAs) and the association of different interactive mechanisms between these ncRNAs with breast carcinogenesis. MicroRNAs (small ncRNAs) and lncRNAs (long ncRNAs) have been explored extensively as classes of ncRNAs in the pathogenesis of several malignancies, including BC. Objective: In this review, we aim to provide a better understanding of the involvement of miRNAs and lncRNAs and their underlying mechanisms in BC development and progression that may assist the development of monitoring biomarkers and therapeutic strategies to effectively combat BC. Conclusion: These ncRNAs play critical roles in cell growth, cell cycle regulation, epithelialmesenchymal transition (EMT), invasion, migration, and apoptosis among others, and were observed to be highly dysregulated in several cancers. The miRNAs and lncRNAs were observed to interact with each other through several mechanisms that governed the expression of their respective targets and could act either as tumor suppressors or as oncogenes, playing a crucial part in breast carcinogenesis.

scholarly journals Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC

2021 ◽  
Author(s):  
Andrew Sulaiman ◽  
Sarah McGarry ◽  
Sai Chilumula ◽  
Rohithk Kandunuri ◽  
Vishak Vinod
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Treatment Strategies ◽  
Major Barrier ◽  
Differential Signal ◽  
Popula Tions ◽  
Novel Treatment Strategies ◽  
Patient Prognosis

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44+/CD24-) and epithelial (ALDHhigh) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these popula-tions remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and discusses novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

scholarly journals FROM EMERGING BIOLOGICAL INSIGHTS TO NOVEL TREATMENT STRATEGIES IN PROSTATE CANCER

2014 ◽  
Author(s):  
Patrizia Limonta ◽  
Roberta M. Moretti ◽  
Stefania Mai ◽  
Monica Marzagalli ◽  
Marcella Motta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Initial Phase ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Gnrh Agonists ◽  
Castration Resistance ◽  
Gnrh Receptors ◽  
Novel Treatment Strategies ◽  
Novel Therapeutic Strategies

Prostate cancer is androgen-dependent in its initial phase. GnRH agonists, through desensitization of pituitary GnRH receptors and subsequent suppression of testosterone secretion, represent the therapy of choice for this pathology. After an initial phase of remission, prostate cancer progresses towards its most aggressive phase of castration-resistance (CRPC). Since conventional chemotherapy treatments (i.e., docetaxel) have provided scant benefit, the identification of the molecular mechanisms underlying prostate cancer progression will definitely help increase the therapeutic options for this almost incurable pathology. Receptors for GnRH agonists are expressed in CRPC cells and their activation significantly inhibit the proliferative and the metastatic behavior of cancer cells, and interferes with the angiogenic process. These data support the notion that locally expressed GnRH receptors represent an effective molecular target for novel therapeutic strategies for CRPC.

Targeting Tumour Metastasis: The Emerging Role of Nanotechnology

2020 ◽  
Vol 27 (8) ◽  
pp. 1367-1381 ◽  
Author(s):  
Sarah Visentin ◽  
Mirela Sedić ◽  
Sandra Kraljević Pavelić ◽  
Krešimir Pavelić
Keyword(s):  
Cancer Progression ◽  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Metastatic Progression ◽  
Therapeutic Concept ◽  
Molecular Alterations ◽  
Tumour Metastasis ◽  
Metastatic Cells ◽  
Metastatic Process ◽  
Underlying Mechanisms

The metastatic process has still not been completely elucidated, probably due to insufficient knowledge of the underlying mechanisms. Here, we provide an overview of the current findings that shed light on specific molecular alterations associated with metastasis and present novel concepts in the treatment of the metastatic process. In particular, we discuss novel pharmacological approaches in the clinical setting that target metastatic progression. New insights into the process of metastasis allow optimisation and design of new treatment strategies, especially in view of the fact that metastatic cells share common features with stem cells. Nano- and micro-technologies are herein elaborated in details as a promising therapeutic concept in targeted drug delivery for metastatic cancer. Progression in the field could provide a more efficient way to tackle metastasis and thus bring about advancements in the treatment and management of patients with advanced cancer.

Exploring PLAC1 Structure and Underlying Mechanisms to Design a Derivative Vaccine Against Breast Cancer Progression; In-Silico Study

2020 ◽  
Vol 17 (5) ◽  
pp. 379-391
Author(s):  
Farzaneh Afzali ◽  
Parisa Ghahremanifard ◽  
Mohammad Mehdi Ranjbar ◽  
Mahdieh Salimi
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
In Silico ◽  
Tertiary Structure ◽  
Specific Antigen ◽  
Docking Simulation ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Underlying Mechanisms

Background: The tolerogenic homeostasis in Breast Cancer (BC) can be surpassed by rationally designed immune-encouraging constructs against tumor-specific antigens through immunoinformatics approach. Objective: Availability of high throughput data providing the underlying concept of diseases and awarded computational simulations, lead to screening the potential medications and strategies in less time and cost. Despite the extensive effects of Placenta Specific 1 (PLAC1) in BC progression, immune tolerance, invasion, cell cycle regulation, and being a tumor-specific antigen the fundamental mechanisms and regulatory factors were not fully explored. It is also worth to design an immune response inducing construct to surpass the hurdles of traditional anti-cancer treatments. Methods and Result: The study was initiated by predicting and modelling the PLAC1 secondary and tertiary structures and then engineering the fusion pattern of PLAC1 derived immunodominant predicted CD8+ and B-cell epitopes to form a multi-epitope immunogenic construct. The construct was analyzed considering the physiochemical characterization, safety, antigenicity, post-translational modification, solubility, and intrinsically disordered regions. After modelling its tertiary structure, proteinprotein docking simulation was carried out to ensure the attachment of construct with Toll-Like Receptor 4 (TLR4) as an immune receptor. To guarantee the highest expression of the designed construct in E. coli k12 as an expressional host, the codon optimization and in-silico cloning were performed. The PLAC1 related miRNAs in BC were excavated and validated through TCGA BC miRNA-sequencing and databases; the common pathways then were introduced as other probable mechanisms of PLAC1 activity. Conclusion: Regarding the obtained in-silico results, the designed anti-PLAC1 multi-epitope construct can probably trigger humoral and cellular immune responses and inflammatory cascades, therefore may have the potential of halting BC progression and invasion engaging predicted pathways.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

Sign in / Sign up

Export Citation Format

Share Document