Cysteine‐rich protein 61 regulates the chemosensitivity of chronic myeloid leukemia to imatinib mesylate through the nuclear factor kappa B/Bcl‐2 pathway

Song, Yanfang; Qi, Lin; Cai, Zhaolian; Hao, Taisen; Zhang, Yaohan; Zhu, Xuyou

doi:10.1111/cas.14083

Cited by 7 publications

(22 citation statements)

References 48 publications

(90 reference statements)

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“…Cysteine-rich protein 61 (Cyr61/CCN1) is a member of the CCN (Cyr61/CTGF/NOV) family and can regulate the survival, adhesion, and migration of various normal cells 3 . Recently, accumulating evidence has revealed that Cyr61 is highly expressed and that the increased Cyr61 level mediates tumor cell growth and metastasis, as well as drug resistance, in cancers 4 - 10 . In CRC patients, high expression of Cyr61 is found in tumor tissues and serum and is related to tumor growth and metastasis and shorter survival times 11 - 15 .…”

Section: Introductionmentioning

confidence: 99%

Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression

et al. 2021

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Although the clinical application of oxaliplatin (L-OHP) has improved the survival of colorectal cancer (CRC) patients, approximately half of patients with CRC fail to achieve good clinical outcomes, indicating resistance to L-OHP therapy. Cysteine-rich protein 61 (Cyr61), a multifunctional extracellular matrix protein, is highly expressed in a variety of tumors; increased Cyr61 expression is known to be closely involved in the chemotherapeutic resistance of many tumors, but its role in the L-OHP resistance of CRC cells has not been studied. In this study, we aimed to investigate the role of Cyr61 in the L-OHP resistance of CRC cells and examine the underlying mechanism. Our findings showed that the mRNA and protein levels of Cyr61 in L-OHP-resistant cells were significantly increased compared with those in nonresistant cells. Knockdown of Cyr61 enhanced the chemosensitivity of L-OHP-resistant cells to L-OHP. Mechanistically, we found that overexpression of Cyr61 decreased L-OHP-induced apoptosis in drug-resistant CRC cells through the regulation of Bcl-xL. Collectively, our results revealed for the first time that Cyr61 plays a crucial role in the resistance of CRC cells to L-OHP and indicated that targeting Cyr61 may be a promising therapeutic strategy to overcome L-OHP resistance in CRC.

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Section: Introductionmentioning

confidence: 99%

Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression

et al. 2021

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“…In (T- and B-) ALL and CML, CCN1 expression has been detected in cell lines, and increased CCN1 levels have been demonstrated in BM-derived mononuclear cells, BM aspirate supernatant, and plasma samples of ALL and CML patients (Cao et al 2019 ; Song et al 2019 ; Zhu et al 2016 ). In ALL, BM and plasma CCN1 levels correlate with the percentage of blasts (Zhu et al 2016 ).…”

Section: Other Ccn Protein Family Membersmentioning

confidence: 99%

“…In ALL, BM and plasma CCN1 levels correlate with the percentage of blasts (Zhu et al 2016 ). In both ALL and CML, CCN1 enhances leukemic cell survival in vitro by decreasing apoptosis through enhanced BCL2 expression via the NF-κB pathway (Song et al 2019 ; Zhu et al 2016 ). In ALL, AKT but not ERK1/2 affects in vitro NF-κB signaling by CCN1 (Zhu et al 2016 ), whereas in CML, AKT nor ERK1/2 are involved in in vitro NF-κB signaling by CCN1 (Song et al 2019 ).…”

Section: Other Ccn Protein Family Membersmentioning

confidence: 99%

“…4 a, b, respectively. CCN1 inhibition increases Imatinib-induced apoptosis of CML cells in vitro and restores the sensitivity of CML cells to Imatinib in vivo (Song et al 2019 ). Similarly, CCN1 decreases Cytarabine chemosensitivity in ALL cells via NF-κB pathway activation, and inhibition of CCN1 can restore ALL cell response to Cytarabine in vitro (Cao et al 2019 ).…”

Section: Other Ccn Protein Family Membersmentioning

confidence: 99%

“…In addition, increased CCN2 and CCN4 levels lead to decreased expression of the pro-apoptotic proteins BIM and BAX, respectively, both resulting in less apoptosis. Furthermore, increased CCN2 levels are associated with decreased p27 expression, thereby affecting cell cycle regulation and restores the sensitivity of CML cells to Imatinib in vivo (Song et al 2019). Similarly, CCN1 decreases Cytarabine chemosensitivity in ALL cells via NF-κB pathway activation, and inhibition of CCN1 can restore ALL cell response to Cytarabine in vitro (Cao et al 2019).…”

Section: Ccn1mentioning

confidence: 99%

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CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment, normal and malignant hematopoiesis

Leguit

Raymakers²,

Hebeda

et al. 2021

J. Cell Commun. Signal.

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CCN2, formerly termed Connective Tissue Growth Factor, is a protein belonging to the Cellular Communication Network (CCN)-family of secreted extracellular matrix-associated proteins. As a matricellular protein it is mainly considered to be active as a modifier of signaling activity of several different signaling pathways and as an orchestrator of their cross-talk. Furthermore, CCN2 and its fragments have been implicated in the regulation of a multitude of biological processes, including cell proliferation, differentiation, adhesion, migration, cell survival, apoptosis and the production of extracellular matrix products, as well as in more complex processes such as embryonic development, angiogenesis, chondrogenesis, osteogenesis, fibrosis, mechanotransduction and inflammation. Its function is complex and context dependent, depending on cell type, state of differentiation and microenvironmental context. CCN2 plays a role in many diseases, especially those associated with fibrosis, but has also been implicated in many different forms of cancer. In the bone marrow (BM), CCN2 is highly expressed in mesenchymal stem/stromal cells (MSCs). CCN2 is important for MSC function, supporting its proliferation, migration and differentiation. In addition, stromal CCN2 supports the maintenance and longtime survival of hematopoietic stem cells, and in the presence of interleukin 7, stimulates the differentiation of pro-B lymphocytes into pre-B lymphocytes. Overexpression of CCN2 is seen in the majority of B-acute lymphoblastic leukemias, especially in certain cytogenetic subgroups associated with poor outcome. In acute myeloid leukemia, CCN2 expression is increased in MSCs, which has been associated with leukemic engraftment in vivo. In this review, the complex function of CCN2 in the BM microenvironment and in normal as well as malignant hematopoiesis is discussed. In addition, an overview is given of data on the remaining CCN family members regarding normal and malignant hematopoiesis, having many similarities and some differences in their function.

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Chemotherapy-initiated cysteine-rich protein 61 decreases acute B-lymphoblastic leukemia chemosensitivity

Shi,

Lin,

Song

et al. 2024

J Cancer Res Clin Oncol

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Purpose Chemoresistance is a major challenge for acute lymphoblastic leukemia (ALL) treatment. Cysteine-rich protein 61 (Cyr61) plays an important role in drug resistance modulation of tumor cells, and Cyr61 levels are increased in the bone marrow of patients with ALL and contribute to ALL cell survival. However, the effect of Cyr61 on B cell acute lymphoblastic leukemia (B-ALL) cell chemosensitivity and the regulatory mechanisms underlying Cyr61 production in bone marrow remain unknown. Methods Nalm-6 and Reh human B-ALL cell lines were used in this study. Cyr61 levels were assessed using quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay. The effect of Cyr61 on B-ALL cell chemosensitivity to daunorubicin (DNR) was evaluated using cell viability and flow cytometry analyses. The regulatory mechanisms of Cyr61 production in bone marrow were examined using qRT-PCR and western blot analysis. Results Cyr61 knockdown and overexpression increased and decreased the chemosensitivity of B-ALL cells to DNR, respectively. Cyr61 attenuated chemotherapeutic drug-induced apoptosis by upregulating B cell lymphoma-2. Notably, DNR induced DNA damage response and increased Cyr61 secretion in B-ALL cells through the ataxia telangiectasia mutated (ATM)-dependent nuclear factor kappa B pathway. Conclusion DNR induces Cyr61 production in B-ALL cells, and increased Cyr61 levels reduce the chemosensitivity of B-ALL cells. Consequently, targeting Cyr61 or related ATM signaling pathway may present a promising treatment strategy to enhance the chemosensitivity of patients with B-ALL.

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Cysteine‐rich protein 61 regulates the chemosensitivity of chronic myeloid leukemia to imatinib mesylate through the nuclear factor kappa B/Bcl‐2 pathway

Cited by 7 publications

References 48 publications

Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression

Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression

CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment, normal and malignant hematopoiesis

Chemotherapy-initiated cysteine-rich protein 61 decreases acute B-lymphoblastic leukemia chemosensitivity

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