The multifunctional role of Notch signaling in multiple myeloma

Sabol, Hayley M.; Delgado‐Calle, Jesús

doi:10.20517/2394-4722.2021.35

Cited by 7 publications

(7 citation statements)

References 111 publications

(168 reference statements)

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“…Although therapeutic approaches to MM have been rapidly evolving, and MM is typically sensitive to a variety of cytotoxic chemotherapies, the prognosis of patients with distal metastasis (the extra-bone MM, at an advanced stage of the disease) is still poor ( 4 – 6 ). Bone destruction is among the most debilitating manifestations of MM and results from the interaction between myeloma cells and the bone marrow microenvironment ( 7 , 8 ). During the malignant transformation of MM, the aggregation and clustering of MM cells increases, which not only breaks through the bone marrow and enters the bone but also eventually forms masses and solid tumor tissues ( 9 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Ran¹,

Xu²,

Wang³

et al. 2022

Front. Oncol.

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Multiple myeloma has a long course, with no obvious symptoms in the early stages. However, advanced stages are characterized by injury to the bone system and represent a severe threat to human health. The results of the present work indicate that the hypermethylation of miR-23 promoter mediates the aberrant expression of uPA/PLAU (urokinase plasminogen activator, uPA) in multiple myeloma cells. miR-23, a microRNA that potentially targets uPA’s 3’UTR, was predicted by the online tool miRDB. The endogenous expressions of uPA and miR-23 are related to disease severity in human patients, and the expression of miR-23 is negatively related to uPA expression. The hypermethylation of the promoter region of miR-23 is a promising mechanism to explain the low level of miR-23 or aberrant uPA expression associated with disease severity. Overexpression of miR-23 inhibited the expression of uPA by targeting the 3’UTR of uPA, not only in MM cell lines, but also in patient-derived cell lines. Overexpression of miR-23 also inhibited in vitro and in vivo invasion of MM cells in a nude mouse model. The results therefore extend our knowledge about uPA in MM and may assist in the development of more effective therapeutic strategies for MM treatment.

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Section: Introductionmentioning

confidence: 99%

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Ran¹,

Xu²,

Wang³

et al. 2022

Front. Oncol.

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“…Additionally, many signaling pathways involved in the growth, proliferation, self-renewal, and differentiation of normal stem cells are abnormally activated or inhibited in tumorigenesis and in cancer initiation and development; these include the Wnt, Notch, NF-κB, and Hedgehog pathways, which regulate CSCs' initial development, and which are all active in a wide range of human cancers, including MM [17]. Moreover, the Notch signaling pathway is deregulated in MM, and preclinical data suggest that this is related to the progression of MM [18].…”

Section: Introductionmentioning

confidence: 99%

Cold Atmospheric Plasma Suppressed MM In Vivo Engraftment by Increasing ROS and Inhibiting the Notch Signaling Pathway

et al. 2022

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Multiple myeloma (MM) is the second most common hematologic malignancy. MM stem cells (MMSCs) are thought to be the main causes of in vivo engraftment and eventual recurrence. As a notable new technology, cold atmospheric plasmas (CAPs) show a promising anti-tumor effect, due to their production of various ROS. In this study, we found that different types of plasma could inhibit MM’s ability to form cell colonies, suppress MM in vivo engraftment, and extend survival times. We demonstrated that NAC (a ROS scavenger) could block ROS increases and reverse the inhibition of MM’s cell-colony-formation ability, which was induced by the plasma treatment. By using a stem cell signaling array, we found that the Notch pathway was inhibited by the plasma treatment; this was further confirmed by conducting real-time PCRs of three MM cell lines. Together, these results constitute the first report of plasma treatment inhibiting MM in vivo engraftment and prolonging survival time by suppressing the Notch pathway via ROS regulation.

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“…Multiple myeloma is a hematologic malignancy of antibody-producing plasma cells in the bone marrow. The disease represents a highly complex and heterogeneous neoplasia (Sabol & Delgado-Calle, 2021).…”

Section: Notch Signaling In Multiple Myelomamentioning

confidence: 99%

“…Multiple myeloma is a hematologic malignancy of antibody‐producing plasma cells in the bone marrow. The disease represents a highly complex and heterogeneous neoplasia (Sabol & Delgado‐Calle, 2021). Previous studies have documented that the Notch signaling pathway is deregulated in multiple myeloma by overexpression of both receptors and ligands.…”

Section: Dysregulation Of Notch Signaling In Bone Marrow and Bone Mal...mentioning

confidence: 99%

Osteohematology: To be or Notch to be

Rothzerg

Erber

Gibbons

et al. 2023

Journal Cellular Physiology

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Osteohematology is an emerging research field that studies the crosstalk between hematopoietic and bone stromal cells, to elucidate the mechanisms of hematological and skeletal malignancies and diseases. The Notch is an evolutionary conserved developmental signaling pathway, with critical roles in embryonic development by controlling cell proliferation and differentiation. However, the Notch pathway is also critically involved in cancer initiation and progression, such as osteosarcoma, leukemia, and multiple myeloma. The Notch‐mediated malignant cells dysregulate bone and bone marrow cells in the tumour microenvironment, resulting in disorders ranging from osteoporosis to bone marrow dysfunction. To date, the complex interplay of Notch signaling molecules in hematopoietic and bone stromal cells is still poorly understood. In this mini‐review, we summarize the crosstalk between cells in bone and bone marrow and their influence under the Notch signaling pathway in physiological conditions and in tumour microenvironment.

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The multifunctional role of Notch signaling in multiple myeloma

Cited by 7 publications

References 111 publications

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Cold Atmospheric Plasma Suppressed MM In Vivo Engraftment by Increasing ROS and Inhibiting the Notch Signaling Pathway

Osteohematology: To be or Notch to be

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