p12CDK2-AP1 interacts with CD82 to regulate the proliferation and survival of human oral squamous cell carcinoma cells

Chai, Jinxiang; Ju, Jun; Zhang, Shaowu; Shen, Zhiyuan; Liang, Liang; Yang, Xiangming; Ni, Qianwei; Sun, Miao

doi:10.3892/or.2016.4893

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…Palmitoylated CD82 specifically recruits interaction partners, including epidermal growth factor receptor, EWI-2, integrin α6, c-Met, and Vangl1, to signaling platforms such as lipid rafts and glycosynapses 56 , 60 , 61 . Furthermore, CD82 interacts with: (i) p12CDK2-AP1 to regulate the proliferation and survival of human oral squamous cell carcinoma cells 57 , (ii) DARC to maintain quiescence in long-term repopulation of hematopoietic stem cells 58 , and (iii) tissue inhibitor of metalloproteinases-1 (TIMP-1), where the proteins colocalize in both pancreatic ductal adenocarcinoma cell lines and clinical samples. Moreover, CD82 facilitates membrane-bound TIMP-1 endocytosis, which significantly contributes to the anti-migration effects of TIMP-1 59 .…”

Section: Discussionmentioning

confidence: 99%

CD82 hypomethylation is essential for tuberculosis pathogenesis via regulation of RUNX1-Rab5/22

Koh

Kim

et al. 2018

Exp Mol Med

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The tumor suppressor gene CD82/KAI1 is a member of the tetraspanin superfamily and organizes various membrane-based processes. Mycobacterium tuberculosis (MTB) persists in host macrophages by interfering with phagolysosome biogenesis and inflammatory responses, but the role of CD82 in controlling the intracellular survival of pathogenic mycobacteria within macrophages remains poorly understood. In this study, we demonstrated that the virulent MTB strain H37Rv (MTB Rv) induced CD82 promoter hypomethylation, resulting in CD82 expression. Targeting of the runt-related transcription factor 1 (RUNX1) by CD82 is essential for phagosome arrest via interacting with Rab5/22. This arrest is required for the intracellular growth of MTB in vitro and in vivo, but not for that of MTB H37Ra (MTB Ra) in macrophages. In addition, knockdown or knockout of CD82 or RUNX1 increased antibacterial host defense via phagolysosome biogenesis, inflammatory cytokine production, and subsequent antimicrobial activity both in vitro and in vivo. Notably, the levels of CD82 and RUNX1 in granulomas were elevated in tuberculosis (TB) patients, indicating that CD82 and RUNX1 have clinical significance in human TB. Our findings identify a previously unrecognized role of CD82 hypomethylation in the regulation of phagosome maturation, enhanced intracellular survival, and the innate host immune response to MTB. Thus, the CD82–RUNX1–Rab5/22 axis may be a previously unrecognized virulence mechanism of MTB pathogenesis.

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Section: Discussionmentioning

confidence: 99%

CD82 hypomethylation is essential for tuberculosis pathogenesis via regulation of RUNX1-Rab5/22

Koh

Kim

et al. 2018

Exp Mol Med

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“…As CDK2-AP1 functions as a specific negative regulator for cyclin-dependent kinase 2 (CDK2) and CDK2 is a checkpoint in the cellular G1/S-phase (48,49), CTSL may be an upstream negative regulator of CDK2-AP1 that proteolytically inactivates CDK2-AP1 and weakens or reverses its inhibition of CDK2. This mechanism may be explained by the observation that CTSL was occasionally detected in normal tissues, but upregulated in the majority of breast cancer tissues associated with malignant progression and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Cathepsin�L interacts with CDK2‑AP1 as a potential predictor of prognosis in patients with breast cancer

et al. 2019

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Cathepsin L (CTSL) is a lysosomal acid cysteine protease that has been implicated in tumorigenesis and malignant progression. In the present study, the role of CTSL in tumorigenesis and prognosis of breast cancer was evaluated. The prognostic value of CTSL was analyzed using immunohistochemistry in patients with breast cancer, as well as online microarray datasets. CTSL expression was knocked down in the breast cancer cell line T-47D using RNA interference. MTT and colony formation assays were performed to assess the role of CTSL in the proliferation of breast cancer cells. Cell cycle progression and apoptosis were measured using flow cytometry. A physical interaction of CTSL and cyclin dependent kinase 2 associated protein 1 (CDK2-AP1) was determined using a glutathione S-transferase pull-down assay. Endogenous CTSL expression was high in breast cancer cells and exhibited an inverse association with CDK2-AP1 expression; aberrant expression of CTSL in breast cancer tissues predicted an improved clinical outcome and prognosis. In addition, CTSL knockdown decelerated the progression of breast cancer cells by arresting cell cycle progression and increasing apoptosis. Thus, CTSL may be a potential therapeutic target for treating patients with breast cancer.

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“…In cancer, several studies have proposed a complex dual role for TSPANs, suggesting that their differential and spatiotemporal expression is associated with either the development and progression of different cancer types (e.g., colorectal [ 31 ], breast [ 32 ], and epithelial ovarian cancer [ 33 ], oral [ 34 , 35 ] and esophageal [ 36 ] squamous cell carcinomas) or providing better clinical outcomes [ 35 , 37 ]. For instance, while the expression of the TSPAN CD81, also known as TSPAN28, in breast cancer, multiple myeloma, and acute myeloid leukemia is considered a marker for worse prognosis, in patients with gallbladder carcinoma, its expression indicates a favorable outcome [ 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis

Ferreira

Almeida

Anjos

et al. 2021

IJMS

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The role and prognostic value of tetraspanins (TSPANs) in vulvar squamous cell carcinoma (VSCC) remain poorly understood. We sought to primarily determine, at both the molecular and tissue level, the expression profile of the TSPANs CD9, CD63, CD81, and CD82 in archived VSCC samples (n = 117) and further investigate their clinical relevance as prognostic markers. Our studies led us to identify CD63 as the most highly expressed TSPAN, at the gene and protein levels. Multicomparison studies also revealed that the expression of CD9 was associated with tumor size, whereas CD63 upregulation was associated with histological diagnosis and vascular invasion. Moreover, low expression of CD81 and CD82 was associated with worse prognosis. To determine the role of TSPANs in VSCC at the cellular level, we assessed the mRNA levels of CD63 and CD82 in established metastatic (SW962) and non-metastatic (SW954) VSCC human cell lines. CD82 was found to be downregulated in SW962 cells, thus supporting its metastasis suppressor role. However, CD63 was significantly upregulated in both cell lines. Silencing of CD63 by siRNA led to a significant decrease in proliferation of both SW954 and SW962. Furthermore, in SW962 particularly, CD63-siRNA also remarkably inhibited cell migration. Altogether, our data suggest that the differential expression of TSPANs represents an important feature for prognosis of VSCC patients and indicates that CD63 and CD82 are likely potential therapeutic targets in VSCC.

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p12CDK2-AP1 interacts with CD82 to regulate the proliferation and survival of human oral squamous cell carcinoma cells

Cited by 3 publications

References 33 publications

CD82 hypomethylation is essential for tuberculosis pathogenesis via regulation of RUNX1-Rab5/22

CD82 hypomethylation is essential for tuberculosis pathogenesis via regulation of RUNX1-Rab5/22

Cathepsin�L interacts with CDK2‑AP1 as a potential predictor of prognosis in patients with breast cancer

Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis

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