scholarly journals Mucin1 and Mucin16: Therapeutic Targets for Cancer Therapy

2021 ◽  
Vol 14 (10) ◽  
pp. 1053
Author(s):  
Dong-Hee Lee ◽  
Seunghyun Choi ◽  
Yoon Park ◽  
Hyung-seung Jin
Keyword(s):  
Cell Growth ◽  
Cancer Therapy ◽  
Immune Evasion ◽  
Human Cancer ◽  
Therapeutic Targets ◽  
Structural Features ◽  
Metabolic Reprogramming ◽  
Cancer Development ◽  
Hallmarks Of Cancer ◽  
Mucus Barrier

The mucin (MUC) family is a group of highly glycosylated macromolecules that are abundantly expressed in mammalian epithelial cells. MUC proteins contribute to the formation of the mucus barrier and thus have protective functions against infection. Interestingly, some MUC proteins are aberrantly expressed in cancer cells and are involved in cancer development and progression, including cell growth, proliferation, the inhibition of apoptosis, chemoresistance, metabolic reprogramming, and immune evasion. With their unique biological and structural features, MUC proteins have been considered promising therapeutic targets and also biomarkers for human cancer. In this review, we discuss the biological roles of the transmembrane mucins MUC1 and MUC16 in the context of hallmarks of cancer and current efforts to develop MUC1- and MUC16-targeted therapies.

scholarly journals A novel chemical inhibitor suppresses breast cancer cell growth and metastasis through inhibiting HPIP oncoprotein

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Pengyun Li ◽  
Shengjie Cao ◽  
Yubing Huang ◽  
Yanan Zhang ◽  
Jie Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cancer Therapy ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Development ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Anticancer Effects

AbstractIncreasing evidence suggests the pivotal role of hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) in cancer development and progression, indicating that HPIP inhibition may be a promising target for cancer therapy. Here, we screened compounds inhibiting breast cancer cell proliferation with HPIP fused with green fluorescent protein as a reporter. A novel agent named TXX-1-10 derived from rimonabant, an antagonist of cannabinoid receptor 1 with anticancer effects, has been discovered to reduce HPIP expression and has greater inhibitory effects on breast cancer cell growth and metastasis in vitro and in vivo than rimonabant. TXX-1-10 regulates HPIP downstream targets, including several important kinases involved in cancer development and progression (e.g., AKT, ERK1/2, and FAK) as well as cell cycle-, apoptosis-, migration-, and epithelial-to-mesenchymal transition (EMT)-related genes. Consistent with the results of anticancer effects, genome-wide RNA sequencing indicated that TXX-1-10 has more significant effects on regulation of the expression of genes related to DNA replication, cell cycle, apoptosis, cell adhesion, cell migration, and invasion than rimonabant. In addition, TXX-1-10 significantly regulated genes associated with the cell growth and extracellular matrix organization, many of which were shown to be regulated by HPIP. Moreover, compared with rimonabant, TXX-1-10 greatly reduces blood-brain barrier penetrability to avoid adverse central depressive effects. These findings suggest that HPIP inhibition may be a useful strategy for cancer treatment and TXX-1-10 is a promising candidate drug for cancer therapy.

scholarly journals Fundamentals of cancer metabolism

2016 ◽  
Vol 2 (5) ◽  
pp. e1600200 ◽  
Author(s):  
Ralph J. DeBerardinis ◽  
Navdeep S. Chandel
Keyword(s):  
Conceptual Framework ◽  
Tumor Cells ◽  
Recent Work ◽  
Cancer Metabolism ◽  
Human Cancer ◽  
Metabolic Reprogramming ◽  
Malignant Cells ◽  
Hallmarks Of Cancer ◽  
Altered Metabolism ◽  
New Strategies

Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer.

scholarly journals Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiao-Xin Sun ◽  
Yanping Li ◽  
Rosalie C. Sears ◽  
Mu-Shui Dai
Keyword(s):  
Cell Growth ◽  
Cancer Therapy ◽  
Tumor Growth ◽  
Protein Stability ◽  
Half Life ◽  
Normal Cell ◽  
Therapeutic Targets ◽  
Degradation Pathway ◽  
Short Half Life ◽  
Ubiquitination Pathway

Deregulated MYC overexpression and activation contributes to tumor growth and progression. Given the short half-life and unstable nature of the MYC protein, it is not surprising that the oncoprotein is highly regulated via diverse posttranslational mechanisms. Among them, ubiquitination dynamically controls the levels and activity of MYC during normal cell growth and homeostasis, whereas the disturbance of the ubiquitination/deubiquitination balance enables unwanted MYC stabilization and activation. In addition, MYC is also regulated by SUMOylation which crosstalks with the ubiquitination pathway and controls MYC protein stability and activity. In this mini-review, we will summarize current updates regarding MYC ubiquitination and provide perspectives about these MYC regulators as potential therapeutic targets in cancer.

scholarly journals AMBRA1 attenuates the proliferation of uveal melanoma cells

Open Medicine ◽  
2021 ◽  
Vol 17 (1) ◽  
pp. 1-14
Author(s):  
Binbin Zhao ◽  
Yun Yang ◽  
Biyun Cun ◽  
Ping Chen
Keyword(s):  
Cell Division ◽  
Cell Growth ◽  
Tumor Suppressor ◽  
Uveal Melanoma ◽  
Human Cancer ◽  
Therapeutic Targets ◽  
E3 Ligase ◽  
Beclin 1 ◽  
Dependent Manner ◽  
The Stability

Abstract Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults with high metastasis rates. D-type cyclins (CCNDs) are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer. Recently, the E3 ligase adaptor, autophagy and beclin 1 regulator 1 (AMBRA1), was reported to regulate the stability of CCNDs, including CCND1, but its role in UVM has not been demonstrated. AMBRA1 is lowly expressed in UVM cells, and the ablation of AMBRA1 promotes the proliferation of 92.1 and OMM1 cells, whereas ectopically expressing AMBRA1 attenuates the proliferation of UVM cells. Further studies found that AMBRA1 promotes the ubiquitination and degradation of CCND1, and AMBRA1 regulates the proliferation of UVM cells in a CCND1-dependent manner. Thus, this study suggests that AMBRA1 serves as an important tumor suppressor by limiting UVM cell growth.

Platelet-Rich and Platelet-Poor Plasma Might Play Supportive Roles in Cancer Cell Culture: A Replacement for Fetal Bovine Serum?

2021 ◽  
Vol 21 ◽  
Author(s):  
Mehdi Talebi ◽  
Mousa Vatanmakanian ◽  
Ali Mirzaei ◽  
Yaghoub Barfar ◽  
Maryam Hemmatzadeh ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Growth ◽  
Cancer Cell ◽  
Human Cancer ◽  
High Price ◽  
Dependent Manner ◽  
Platelet Poor Plasma ◽  
Protein Levels ◽  
Healthy Donors ◽  
Regulatory Functions

Background: Platelet-rich (PRP) and Platelet-poor plasma (PPP) are widely used in research and clinical platforms mainly due to their capacities to enhance cell growth. Although short half-life (5 days) and the high price of platelet products pose challenges regarding their usage, they maintain the growth regulatory functions for weeks. Thus, we aimed to assess the supplementary values of these products in human CCRF-CEM cancer cells. Mechanistically, we also checked if the PRP/PPP treatment enhances YKL-40 expression as a known protein regulating cell growth. Methods: The PRP/PPP was prepared from healthy donors using manual stepwise centrifugation and phase separation. The viability of the cells treated with gradient PRP/PPP concentrations (2, 5, 10, and 15%) was measured by the MTT assay. The YKL-40 mRNA and protein levels were assessed using qRT-PCR and western blotting. The data were compared to FBS-treated cells. Result: Our findings revealed that the cells treated by PRP/PPP not only were morphologically comparable to those treated by FBS but also, they showed greater viability at the concentrations of 10 and 15%. Moreover, it was shown that PRP/PPP induce cell culture support, at least in part, via inducing YKL-40 expression at both mRNA and protein levels in a time- and dose-dependent manner. Conclusion: Collectively, by showing cell culture support comparable to FBS, the PRP/PPP might be used as good candidates to supplement the cancer cell culture and overcome concerns regarding the use of FBS as a non-human source in human cancer research.

scholarly journals Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuanjun Lu ◽  
Yau-Tuen Chan ◽  
Hor-Yue Tan ◽  
Sha Li ◽  
Ning Wang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Epigenetic Regulation ◽  
Potential Role ◽  
Human Cancer

scholarly journals Crk and CrkL as Therapeutic Targets for Cancer Treatment

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 739
Author(s):  
Taeju Park
Keyword(s):  
Tumor Cell ◽  
Cancer Treatment ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Therapeutic Targets ◽  
Viral Oncoprotein ◽  
Mesenchymal Transition ◽  
Chemotherapy Drugs ◽  
Cell Functions

Crk and CrkL are cellular counterparts of the viral oncoprotein v-Crk. Crk and CrkL are overexpressed in many types of human cancer, correlating with poor prognosis. Furthermore, gene knockdown and knockout of Crk and CrkL in tumor cell lines suppress tumor cell functions, including cell proliferation, transformation, migration, invasion, epithelial-mesenchymal transition, resistance to chemotherapy drugs, and in vivo tumor growth and metastasis. Conversely, overexpression of tumor cells with Crk or CrkL enhances tumor cell functions. Therefore, Crk and CrkL have been proposed as therapeutic targets for cancer treatment. However, it is unclear whether Crk and CrkL make distinct or overlapping contributions to tumor cell functions in various cancer types because Crk or CrkL have been examined independently in most studies. Two recent studies using colorectal cancer and glioblastoma cells clearly demonstrated that Crk and CrkL need to be ablated individually and combined to understand distinct and overlapping roles of the two proteins in cancer. A comprehensive understanding of individual and overlapping roles of Crk and CrkL in tumor cell functions is necessary to develop effective therapeutic strategies. This review systematically discusses crucial functions of Crk and CrkL in tumor cell functions and provides new perspectives on targeting Crk and CrkL in cancer therapy.

scholarly journals Arginine Methyltransferase PRMT1 Regulates p53 Activity in Breast Cancer

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 789
Author(s):  
Li-Ming Liu ◽  
Qiang Tang ◽  
Xin Hu ◽  
Jing-Jing Zhao ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Asymmetric Dimethylarginine ◽  
Human Cancer ◽  
Specific Inhibitor ◽  
Dependent Manner ◽  
Breast Tumorigenesis ◽  
Stress Signals

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.

scholarly journals Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 359
Author(s):  
Hsiang-Hao Chuang ◽  
Yen-Yi Zhen ◽  
Yu-Chen Tsai ◽  
Cheng-Hao Chuang ◽  
Ming-Shyan Huang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Tumor Suppressors ◽  
Protein Conformation ◽  
Genome Stability ◽  
Recent Progress ◽  
Multiple Roles ◽  
Cancer Development ◽  
Cancer Hallmarks ◽  
Underlying Mechanisms ◽  
And Function

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.

scholarly journals Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1792
Author(s):  
Debashri Manna ◽  
Devanand Sarkar
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Development ◽  
Epigenetic Alterations ◽  
Hallmarks Of Cancer ◽  
Comprehensive Description ◽  
Molecular Abnormalities ◽  
Selective Pressures ◽  
Resistance To Chemotherapy

Cancer development results from the acquisition of numerous genetic and epigenetic alterations in cancer cells themselves, as well as continuous changes in their microenvironment. The plasticity of cancer cells allows them to continuously adapt to selective pressures brought forth by exogenous environmental stresses, the internal milieu of the tumor and cancer treatment itself. Resistance to treatment, either inherent or acquired after the commencement of treatment, is a major obstacle an oncologist confronts in an endeavor to efficiently manage the disease. Resistance to chemotherapy, chemoresistance, is an important hallmark of aggressive cancers, and driver oncogene-induced signaling pathways and molecular abnormalities create the platform for chemoresistance. The oncogene Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) is overexpressed in a diverse array of cancers, and its overexpression promotes all the hallmarks of cancer, such as proliferation, invasion, metastasis, angiogenesis and chemoresistance. The present review provides a comprehensive description of the molecular mechanism by which AEG-1 promotes tumorigenesis, with a special emphasis on its ability to regulate chemoresistance.

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