Expression of Spy1 protein in human Non-Hodgkin’s Lymphomas is correlated with phosphorylation of p27Kip1 on Thr187 and cell proliferation

Hang, Qinglei; Fei, Min; Hou, Sicong; Ni, Qing; Lu, Cuihua; Zhang, Guowei; Gong, Peipei; Guan, Chengqi; Huang, Xing‐Huai; He, Song

doi:10.1007/s12032-012-0224-x

Cited by 26 publications

(16 citation statements)

References 39 publications

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“…18,[25][26][27][28] In this present study, we have demonstrated that abrogating direct interactions between Spy1 and either p27 or Cdk2 significantly decreases the rate of tumorigenesis and overall tumor size in vivo. Low levels of p27 protein has been implicated in many human cancers including breast 29 and is found to correlate with poor patient outcome.…”

Section: Role Of Spy1-p27 Binding In Tumorigenesissupporting

confidence: 56%

Direct interactions with both p27 and Cdk2 regulate Spy1-mediated proliferationin vivoandin vitro

et al. 2016

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Families of cyclin-like proteins have emerged that bind and activate cyclin dependent kinases (Cdk)s, directing the phosphorylation of noncanonical Cdk substrates. One of these proteins, Spy1, has demonstrated the unique ability to directly bind and activate both Cdk1 and Cdk2, as well as binding and promoting the degradation of at least one Cdk inhibitor, p27 Kip1 . Spy1 accelerates somatic cell growth and proliferation and is implicated in a number of human cancers including the breast, brain and liver. Herein we isolate key residues mediating the direct interaction with p27. We use mutants of Spy1 to determine the physiological role of direct interactions with distinct binding partners Cdk2 and p27. We demonstrate that disrupting the direct interaction with either Spy1 binding partner decreased endogenous activity of Cdk2, as well as Spy1-mediated proliferation. However, only the direct interaction with p27 was essential for Spy1-mediated effects on p27 stability. In vivo neither mutation completely prevented tumorigenesis, although each mutation slowed the rate of Spy1-mediated tumorigenesis and decreased overall tumor volumes. This work supports the conclusion that direct interaction with both p27 and Cdk2 contribute to Spy1-mediated effects on cell growth. It is important to elucidate the dynamics of these interactions and to consider these data when assessing functional outcomes.

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Section: Role Of Spy1-p27 Binding In Tumorigenesissupporting

confidence: 56%

Direct interactions with both p27 and Cdk2 regulate Spy1-mediated proliferationin vivoandin vitro

et al. 2016

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“…Immunoprecipitation was performed as described previously [15]. Briefly, total cell lysates was incubated with anti-p27 Kip1 antibody or control IgG (Santa Cruz Biotechnology, USA) at 4°C overnight.…”

Section: Immunoprecipitationmentioning

confidence: 99%

Overexpression of TRIP6 promotes tumor proliferation and reverses cell adhesion-mediated drug resistance (CAM-DR) via regulating nuclear p27Kip1 expression in non-Hodgkin’s lymphoma

Miao

et al. 2015

Tumor Biol.

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Recent studies have identified that thyroid hormone receptor-interacting protein 6 (TRIP6) is implicated in tumorigenesis. However, the functional role of TRIP6 in non-Hodgkin's lymphoma (NHL) has never been elucidated. In this study, we demonstrated that TRIP6 is reversely correlated with the clinical outcomes of NHL patients. Western blot and immunohistochemical analysis revealed that TRIP6 expression is lower in indolent lymphoma than in progressive lymphoma. Kaplan-Meier survival curves indicated that the upregulation of TRIP6 is significantly associated with poor overall survival. Moreover, patients with higher expression of TRIP6 are prone to shorter time to recurrence. Furthermore, we also found that TRIP6 can promote the proliferation of NHL cells via regulating cell cycle progression. In addition, adhesion of lymphoma cells to fibronectin (FN) decreased TRIP6 expression, which led to the upregulation of nuclear p27(Kip1) expression by decreasing phosphorylation of p27(Kip1) at T157. Importantly, overexpression of TRIP6 can reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype in NHL. In summary, these results suggest that TRIP6 is a novel prognostic indicator for NHL patients and may shed new insights into the important role of TRIP6 in cancer development.

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“…It has been previously reported that LIMD1 may inhibit S-phase progression in mammalian cells, by downregulating cellular factors necessary for transition from the G 0 /G 1 to S phase of the cell cycle (15). In hematologic malignancies, accumulating data suggest that cell cycle arrest may contribute to the CAM-DR phenotype (16)(17)(18). Therefore, the present study investigated whether LIMD1 can also affect cell cycle progression and CAM-DR in NHL.…”

Section: Introductionmentioning

confidence: 96%

Silencing of LIMD1 promotes proliferation and reverses cell adhesion‑mediated drug resistance in non‑Hodgkin's lymphoma

et al. 2019

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LIM domains-containing protein 1 (LIMD1) is a tumor suppressor protein downregulated in numerous solid malignancies. However, the functional role of LIMD1 in non-Hodgkin's lymphoma (NHL) remains unclear. In the present study, it was demonstrated that LIMD1 is associated with the proliferation of NHL and cell adhesion mediated-drug resistance (CAM-DR). It was indicated by western blot analysis that LIMD1expression is lower in progressive lymphoma compared with indolent lymphoma. Furthermore, it was indicated that the role of LIMD1 in cell viability and proliferation remains unclear. Finally, the present study demonstrated that LIMD1 serves an important role in CAM-DR by regulating cell cycle progression. Silencing of LIMD1 may reverse CAM-DR in NHL. Therefore, the findings of the present study suggested that LIMD1 may be a potential therapeutic target for patients with NHL.

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Expression of Spy1 protein in human Non-Hodgkin’s Lymphomas is correlated with phosphorylation of p27Kip1 on Thr187 and cell proliferation

Cited by 26 publications

References 39 publications

Direct interactions with both p27 and Cdk2 regulate Spy1-mediated proliferationin vivoandin vitro

Direct interactions with both p27 and Cdk2 regulate Spy1-mediated proliferationin vivoandin vitro

Overexpression of TRIP6 promotes tumor proliferation and reverses cell adhesion-mediated drug resistance (CAM-DR) via regulating nuclear p27Kip1 expression in non-Hodgkin’s lymphoma

Silencing of LIMD1 promotes proliferation and reverses cell adhesion‑mediated drug resistance in non‑Hodgkin's lymphoma

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