Epigenetic regulation of CXCR4 signaling in cancer pathogenesis and progression

Alsayed, Reem Khaled M E; Khan, Abdul Quaiyoom; Faried, Ahmad; Ansari, Abdul Wahid; Alam, Majid; Buddenkotte, Jorg; Steinhoff, Martin; Uddin, Shahab; Ahmad, Aamir

doi:10.1016/j.semcancer.2022.03.019

Cited by 22 publications

(12 citation statements)

References 143 publications

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“…This suggests that mRNA splicing regulation based on RNA post-transcription regulation has an important influence on the specific function and activity of CXCL12. As the receptor of CXCL12, CXCR4 is also dysregulated through epigenetic regulation [ 98 ]. For example, miR-494-3p has been shown to inhibit CXCR4 expression after transcription processes in prostate cancer [ 99 ]; lncRNA UCA1 activates CXCR4 through inhibiting the activity of miR-204 to promote the progression of prostate cancer [ 100 ].…”

Section: Epigenetic Modifications In Tumor Microenvironment (Tme)mentioning

confidence: 99%

Epigenetic Modifications in Prostate Cancer Metastasis and Microenvironment

Zhang

Shen

Zeng

2023

Cancers

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The gradual evolution of prostate tissue from benign tumor to malignant lesion or distant metastasis is driven by intracellular epigenetic changes and the tumor microenvironment remodeling. With the continuous study of epigenetic modifications, these tumor-driving forces are being discovered and are providing new treatments for cancer. Here we introduce the classification of epigenetic modification and highlight the role of epigenetic modification in tumor remodeling and communication of the tumor microenvironment.

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Section: Epigenetic Modifications In Tumor Microenvironment (Tme)mentioning

confidence: 99%

Epigenetic Modifications in Prostate Cancer Metastasis and Microenvironment

Zhang

Shen

Zeng

2023

Cancers

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“…C‐X‐C‐motif chemokine receptor 4 (CXCR4) is a G‐protein‐coupled receptor involved in a number of physiological processes in the hematopoietic and immune systems and also has important roles in promoting tumor cell proliferation, metastasis, and angiogenesis. 599 , 600 CXCR4 is found to be a prognostic marker in many different cancers, including leukemia, breast, lung, prostate, ovarian and CRC, where the stromal cell‐derived factor‐1 (SDF‐1)/CXCR4 axis (also called CXCL12/CXCR4 axis) initiates divergent signaling pathways, including PI3K/AKT, MAPK, and JAK/STAT signals, which can result in a variety of responses such as chemotaxis, cell survival and/or proliferation, increase in intracellular calcium, and gene transcription. 601 , 602 In addition, the organs and tissues that possess high levels of SDF‐1, such as liver, lung, bone marrow, and lymph nodes, attract the migration of CXCR4‐expressing cancer cells.…”

Section: Selective Small Molecule Nonkinase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors targeting the cancers

Liu

Chen

Zhang

et al. 2022

MedComm

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Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatment still face many obstacles, such as low response rate, short duration of response, toxicity, biomarkers, and resistance. To better promote the development of small molecule inhibitors targeting cancers, we comprehensively reviewed small molecule inhibitors involved in all the approved agents and pivotal drug candidates in clinical trials arranged by the signaling pathways and the classification of small molecule inhibitors. We discussed lessons learned from the development of these agents, the proper strategies to overcome resistance arising from different mechanisms, and combination therapies concerned with small molecule inhibitors. Through our review, we hoped to provide insights and perspectives for the research and development of small molecule inhibitors in cancer treatment.

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“…Indeed, we demonstrate that the transgenic thymus is mostly populated by immature CD3e + T-cells with a reduced expression of CXCR4 and, typical to human T-ALL (3,23,24) of CD5. Multiple molecular types of machinery regulate CXCR4 expression, by implying transcription factors like E2A and NF-kB (25)(26)(27) or epigenetic post-transcriptional regulators of CXCR4 (28)(29)(30). MicroRNAs (miRNAs) play an essential role during both normal and malignant haematopoiesis (31); some of them are up-or down-regulated in patients with haematological malignancies, including T-ALL (32,33).…”

Section: Introductionmentioning

confidence: 99%

Notch3-regulated microRNAs impair CXCR4-dependent maturation of thymocytes allowing maintenance and progression of T-ALL

Felli,

Sergio,

Gaizo

et al. 2023

Preprint

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Malignant transformation of T-cell progenitors causes T-cell acute lymphoblastic leukemia (T-ALL), an aggressive childhood lymphoproliferative disorder. Activating mutations of Notch1 and overexpression of Notch3, as well as rare Notch3 activating mutations have been detected in T-ALL patients. In this study, we aimed to deeply characterize major steps contributing to the progression of T-ALL: hyperactive Notch3-related pathways involved in T-cell dynamics within the thymus and bone marrow infiltration by immature thymocyte subpopulations. We previously generated a transgenic T-ALL mouse model (N3-ICtg) demonstrating that aberrant Notch3 signaling affects early thymocyte maturation programs and leads to bone marrow infiltration by CD4⁺CD8⁺ (DP) T-cells Notch3highCXCR4high. Newly, our in vivo results suggest that an anomalous immature thymocyte subpopulation, such as CD4-CD8- (DN) over-expressing CD3ε, but with low CD5 and CXCR4 expression, dominates N3-ICtg thymus-resident DN subset in T-ALL progression. MicroRNAs might be of significance in T-ALL pathobiology, however, whether required for leukemia maintenance is not fully understood. The selection of specific DN subsets demonstrates the inverse correlation between CXCR4 expression and a panel of Notch3-deregulated miRNAs. Interestingly, we found that hyperactive Notch3 targets CXCR4 expression through the cooperative effects of miR-139-5p and miR-150-5p, and impairs thymocyte differentiation which increases DNCD3ε+CD25+CXCR4- cells that improperly colonize the transgenic BM. These data point out that Notch3 selects specific immature T-cells within the thymus, a reservoir to sustain T-ALL progression.

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Epigenetic regulation of CXCR4 signaling in cancer pathogenesis and progression

Cited by 22 publications

References 143 publications

Epigenetic Modifications in Prostate Cancer Metastasis and Microenvironment

Epigenetic Modifications in Prostate Cancer Metastasis and Microenvironment

Small molecule inhibitors targeting the cancers

Notch3-regulated microRNAs impair CXCR4-dependent maturation of thymocytes allowing maintenance and progression of T-ALL

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