Breast cancer: understanding etiology, addressing molecular signaling pathways, identifying therapeutic targets and strategizing the treatment

2021 ◽  
Vol 12 (3) ◽  
pp. 1757-1769
Author(s):  
Preeti Tanaji Mane ◽  
Sangram Prakash Patil ◽  
Balaji Sopanrao Wakure ◽  
Pravin Shridhar Wakte
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Treatment Options ◽  
Current Treatment ◽  
Vital Role ◽  
Molecular Signaling ◽  
Breast Tumorigenesis ◽  
Non Coding Rnas ◽  
Cycle Regulation

Breast cancer has messed the life of a greater number of women being the most common cancer affecting them worldwide. A number of risk factors contribute the breast malignancy, however, genetic drift is accountable the most. Depending on the cell origin, invasiveness and receptors involved, breast cancer is classified into various subtypes. The accurate diagnosis of breast cancer is important as it defines the prognosis and directs the type of treatment required. A number of major signaling pathways involved in breast tumorigenesis and its development include estrogen receptors (ERs), HER2, Wnt/β-catenin, Notch, Hedgehog (Hh), PI3K and mTOR pathway. Furthermore, certain enzymes like Cyclin dependent kinases and breast tumor kinases also play a vital role in cell cycle regulation and therefore, in the development of breast neoplasms. Recent studies have also enlightened the role of non-coding RNAs in breast cancer development. This review discusses various aspects of breast cancer such as its etiology, subtypes, various signaling pathways involved, targets projected by these pathways and the current treatment options based on a few of these targets. Also, the role of different genes, enzymes and non-coding RNAs related to breast tumorigenesis and development is discussed.

Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

2020 ◽  
Author(s):  
Shamim Mushtaq
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Web Of Science ◽  
The Body ◽  
Main Role ◽  
Hallmarks Of Cancer ◽  
Cyclin Dependent Kinases ◽  
Tumor Studies ◽  
Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

MicroRNAs as Biomarker for Breast Cancer

2020 ◽  
Vol 20 (10) ◽  
pp. 1597-1610 ◽  
Author(s):  
Taru Aggarwal ◽  
Ridhima Wadhwa ◽  
Riya Gupta ◽  
Keshav Raj Paudel ◽  
Trudi Collet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Association Studies ◽  
Large Family ◽  
Breast Cancer Diagnosis ◽  
Cell Multiplication ◽  
Cell Physiology ◽  
Gene Transcript ◽  
Genome Wide Association Studies ◽  
Non Coding Rnas

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.

scholarly journals Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3427
Author(s):  
Reyhaneh Farghadani ◽  
Rakesh Naidu
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Mapk Pathway ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Drug Candidate ◽  
Molecular Signaling ◽  
Her2 Positive ◽  
Therapeutic Implications ◽  
Epidermal Growth

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Despite the overall successes in breast cancer therapy, hormone-independent HER2 negative breast cancer, also known as triple negative breast cancer (TNBC), lacking estrogens and progesterone receptors and with an excessive expression of human epidermal growth factor receptor 2 (HER2), along with the hormone-independent HER2 positive subtype, still remain major challenges in breast cancer treatment. Due to their poor prognoses, aggressive phenotype, and highly metastasis features, new alternative therapies have become an urgent clinical need. One of the most noteworthy phytochemicals, curcumin, has attracted enormous attention as a promising drug candidate in breast cancer prevention and treatment due to its multi-targeting effect. Curcumin interrupts major stages of tumorigenesis including cell proliferation, survival, angiogenesis, and metastasis in hormone-independent breast cancer through the modulation of multiple signaling pathways. The current review has highlighted the anticancer activity of curcumin in hormone-independent breast cancer via focusing on its impact on key signaling pathways including the PI3K/Akt/mTOR pathway, JAK/STAT pathway, MAPK pathway, NF-ĸB pathway, p53 pathway, and Wnt/β-catenin, as well as apoptotic and cell cycle pathways. Besides, its therapeutic implications in clinical trials are here presented.

scholarly journals Role of the NUDT Enzymes in Breast Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2267
Author(s):  
Roni H. G. Wright ◽  
Miguel Beato
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Breast Cancers ◽  
Metastatic Colonization ◽  
Hormone Receptor Positive ◽  
Aggressive Cancer ◽  
Cancer Types ◽  
Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

scholarly journals Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3357
Author(s):  
Hongmei Zheng ◽  
Sumit Siddharth ◽  
Sheetal Parida ◽  
Xinhong Wu ◽  
Dipali Sharma
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Combined Treatment ◽  
High Mobility ◽  
Sphingosine 1 Phosphate ◽  
Molecular Patterns

Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

scholarly journals A Review on the Carcinogenic Roles of DSCAM-AS1

2021 ◽  
Vol 9 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Tayyebeh Khoshbakht ◽  
Mohammad Taheri ◽  
Kaveh Ebrahimzadeh
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Antisense Rna ◽  
Breast Tumor ◽  
Cancer Colorectal ◽  
Small Cell ◽  
Small Cell Lung ◽  
Breast Tumor Cells ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are a group of transcripts with fundamental roles in the carcinogenesis. DSCAM Antisense RNA 1 (DSCAM−AS1) is an example of this group of transcripts which has been firstly identified in an attempt to find differentially expressed transcripts between breast tumor cells and benign breast samples. The pathogenic roles of DSCAM-AS1 have been vastly assessed in breast cancer, yet its roles are not restricted to this type of cancer. Independent studies in non-small cell lung cancer, colorectal cancer, osteosarcoma, hepatocellular carcinoma, melanoma and cervical cancer have validated participation of DSCAM-AS1 in the carcinogenic processes. miR-577, miR-122-5p, miR-204-5p, miR-136, miR−137, miR−382, miR−183, miR−99, miR-3173-5p, miR-874-3p, miR-874-3p, miR-150-5p, miR-2467-3p, miR-216b, miR-384, miR-186-5p, miR-338-3p, miR-877-5p and miR-101 are among miRNAs which interact with DSCAM-AS1. Moreover, this lncRNA has interactions with Wnt/β-catenin pathway. The current study aims at summarization of the results of studies which focused on the assessment of oncogenic role of DSCAM-AS1.

scholarly journals USP7 Inhibition Alleviates H2O2-Induced Injury in Chondrocytes via Inhibiting NOX4/NLRP3 Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Gang Liu ◽  
Qingbai Liu ◽  
Bin Yan ◽  
Ziqiang Zhu ◽  
Yaozeng Xu
Keyword(s):  
Treatment Options ◽  
Current Treatment ◽  
Pathological Process ◽  
Joint Disease ◽  
Matrix Remodeling ◽  
Ros Production ◽  
Caspase 1 ◽  
Enhanced Production

Osteoarthritis (OA), the most common form of arthritis, is a very common joint disease that often affects middle-aged to elderly people. However, current treatment options for OA are predominantly palliative. Thus, understanding its pathological process and exploring its potential therapeutic approaches are of great importance. Rat chondrocytes were isolated and exposed to hydrogen peroxide (H2O2) to mimic OA. The effects of H2O2 on ubiquitin-specific protease 7 (USP7) expression, reactive oxygen species (ROS) levels, proliferation, inflammatory cytokine release, and pyroptosis were measured. USP7 was knocked down (KD) or overexpressed to investigate the role of USP7 in OA. Co-immunoprecipitation (Co-IP) was used to study the interaction between USP7 and NAD(P)H oxidases (NOX)4 as well as NOX4 ubiquitination. NOX4 inhibitor was applied to study the involvement of NOX4 in USP7-mediated OA development. USP7 inhibitor was given to OA animals to further investigate the role of USP7 in OA in vivo. Moreover, H2O2 treatment significantly increased USP7 expression, enhanced ROS levels, and inhibited proliferation in rat chondrocytes. The overexpression of USP7 enhanced pyroptosis, ROS production, interleukin (IL)-1β and IL-18 levels, and the expression level of NLRP3, GSDMD-N, active caspase-1, pro-caspase-1, matrix metalloproteinases (MMP) 1, and MMP13, which was abolished by ROS inhibition. The USP7 KD protected rat chondrocytes against H2O2-induced injury. Co-IP results showed that USP7 interacted with NOX4, and USP7 KD enhanced NOX4 ubiquitinylation. The inhibition of NOX4 blocked the pro-OA effect of USP7. Moreover, the USP7 inhibitor given to OA animals suppressed OA in vivo. USP7 inhibited NOX4 ubiquitination for degradation which leads to elevated ROS production. ROS subsequently activates NLPR3 inflammasome, leading to enhanced production of IL-1β and IL-18, GSDMD-N-dependent pyroptosis, and extracellular matrix remodeling. Thus, UPS7 contributes to the progression of OA via NOX4/ROS/NLPR3 axis.

scholarly journals Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Chong Lu ◽  
Xiuhua Wang ◽  
Xiangwang Zhao ◽  
Yue Xin ◽  
Chunping Liu
Keyword(s):  
Breast Cancer ◽  
Normal Breast ◽  
Tumor Promoter ◽  
Women Health ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Migration ◽  
Breast Tissues ◽  
Long Non Coding Rna

Abstract Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

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