The Cytosolic Chaperonin CCT/TRiC and Cancer Cell Proliferation

Boudiaf-Benmammar, Chafika; Cresteil, Thierry; Melki, Ronald

doi:10.1371/journal.pone.0060895

Cited by 69 publications

(58 citation statements)

References 39 publications

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“…Its expression is regulated by the signaling downstream tot the PI3K pathway. According to recent data, the TCPA appears necessary for the in vitro and in vivo survival and growth of breast cancer cells [165,166]. An increased level of it (2.5x) was detected in the tumors.…”

Section: Tcp-1-alpha Tcpa (Tcp1)mentioning

confidence: 97%

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Pucci‐Minafra¹,

Cara²,

Musso³

et al. 2017

Preprint

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Abstract:The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing postsurgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.

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Section: Tcp-1-alpha Tcpa (Tcp1)mentioning

confidence: 97%

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Pucci‐Minafra¹,

Cara²,

Musso³

et al. 2017

Preprint

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“…Reduction of the CCT or CCT subunit could result in growth arrest, with significant alterations in cell morphology and motility [14]. Moreover, the CCT proteins promote the development of several tumor types, including breast cancer [4], colorectal cancer [7,24,27,28], uterine sarcoma [21], lung carcinoma [8,24], ovarian cancer [22], and multitudinous tumor cells [1,25]. Recent studies have suggested that CCT8 might be upregulated in colon, breast and hepatocellular carcinoma specimens [17,35,36].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of CCT8 and its significance for tumor cell proliferation, migration and invasion in glioma

Qiu

Huang

et al. 2015

Pathology - Research and Practice

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“…Furthermore, TRiC has been suggested to play a role in cancer cell development by modulating the folding and activity of client proteins involved in oncogenesis, such as the tumor suppressor proteins Von Hippel-Lindau (VHL) (20,21) and p53 (22), as well as the prooncogenic protein STAT3 (signal transducer and activator of transcription 3) (23). Of note, the expression levels of TRiC in leukemic cells are higher than in normal hematopoietic cells (24), suggesting a potential contribution of TRiC to leukemogenesis through its interactions with leukemia-causing oncoproteins.…”

mentioning

confidence: 99%

Chaperonin TRiC/CCT Modulates the Folding and Activity of Leukemogenic Fusion Oncoprotein AML1-ETO

Roh¹,

Kasembeli

Galaz-Montoya³

et al. 2016

Journal of Biological Chemistry

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AML1-ETO is the most common fusion oncoprotein causing acute myeloid leukemia (AML), a disease with a 5-year survival rate of only 24%. AML1-ETO functions as a rogue transcription factor, altering the expression of genes critical for myeloid cell development and differentiation. Currently, there are no specific therapies for AML1-ETO-positive AML. While known for decades to be the translational product of a chimeric gene created by the stable chromosome translocation t(8;21)(q22;q22), it is not known how AML1-ETO achieves its native and functional conformation or whether this process can be targeted for therapeutic benefit. Here, we show that the biosynthesis and folding of the AML1-ETO protein is facilitated by interaction with the essential eukaryotic chaperonin TRiC (or CCT). We demonstrate that a folding intermediate of AML1-ETO binds to TRiC directly, mainly through its ␤-strand rich, DNA-binding domain (AML-(1-175)), with the assistance of HSP70. Our results suggest that TRiC contributes to AML1-ETO proteostasis through specific interactions between the oncoprotein's DNA-binding domain, which may be targeted for therapeutic benefit.Acute myeloid leukemia (AML) 4 is characterized by the uncontrolled proliferation and incomplete differentiation of a malignant clone of myeloid stem or progenitor cells (1). The majority of cases can be categorized based on the stable, nonrandom chromosome translocation they contain. The most common translocation in AML is t(8;21)(q22;q22), which juxtaposes portions of two genes, AML1 and ETO, generating the fusion oncoprotein AML1-ETO (2). The AML1 gene encodes a critical transcription factor that regulates a variety of genes involved in proliferation and differentiation of many cell types, including those within the hematopoietic system (3, 4). On the other hand, the ETO (eight twenty-one) protein is a protein harboring transcriptional repressor activities (5). The DNAbinding domain of AML1 is located within the amino-terminal portion of AML1-ETO and is fused in-frame to portions of the ETO gene containing dimerization and zinc finger motifs shown to interact with nuclear receptor co-repressors such as the N-CoR (nuclear receptor co-repressor)/SMRT (silencing mediator for retinoid and thyroid receptors) complex and HDAC (histone deacetylase) (6 -8). Thus, AML1-ETO functions as a rogue transcriptional repressor, rather than as a transcriptional activator.Unfortunately, there are currently no specific treatments for AML1-ETO-positive leukemia and the prognosis for this disease remains dismal. However, it has been shown that targeting of AML1-ETO using small interfering RNAs (siRNAs) supports normal myeloid differentiation of t(8;21)-positive leukemic cells (9), which highlights AML1-ETO as a direct clinical target to treat AML. Interestingly, inhibition of heat shock protein 70/90 (HSP70/90), two major proteostasis regulators, has shown antileukemic effects in AML1-ETO-positive cells (10, 11), suggesting that AML1-ETO might rely on chaperones to fold and function properly. Howe...

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The Cytosolic Chaperonin CCT/TRiC and Cancer Cell Proliferation

Cited by 69 publications

References 39 publications

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Overexpression of CCT8 and its significance for tumor cell proliferation, migration and invasion in glioma

Chaperonin TRiC/CCT Modulates the Folding and Activity of Leukemogenic Fusion Oncoprotein AML1-ETO

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