Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme

Ding, Yin; Chen, Weikai; O’Kelly, James; Lu, Daning; Ham, Michelle; Doan, Ngan; Xie, Dong; Wang, Charles; Vadgama, Jay; Said, Jonathan W.; Black, Keith L.; Koeffler, H. Phillip

doi:10.1002/ijc.25257

Cited by 49 publications

(56 citation statements)

References 29 publications

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“…In GBM, such a key gene could be CTGF, which is involved in GBM pathogenesis via its effects on cell migration (Demuth et al 2008), proliferation, angiogenesis, and multidrug resistance (Yin et al 2010). Importantly, CTGF expression is known to be associated with GBM progression and poor patient survival (Xie et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…CTGF is overexpressed in ∼58% of primary GBM compared with normal brain tissue, and its expression is associated with disease progression and poor patient survival (Xie et al 2004). Forced overexpression of CTGF in GBM cell lines has been shown to increase in vitro cell migration (Demuth et al 2008), proliferation, and resistance to tumor drugs, as well as increase tumor size and vascularization in vivo (Yin et al 2010). Because CTGF expression is both important for GBM malignancy and significantly anti-correlated with that of miR-17∼92 in human cancers, we postulated that GBM may maintain low levels of miR-17∼92 to allow unfettered expression of CTGF.…”

Section: Introductionmentioning

confidence: 97%

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Targeting of TGFβ signature and its essential component CTGF by miR-18 correlates with improved survival in glioblastoma

Fox

Dews

Minn

et al. 2012

RNA

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The miR-17∼92 cluster is thought to be an oncogene, yet its expression is low in glioblastoma multiforme (GBM) cell lines. This could allow unfettered expression of miR-17∼92 target genes such as connective tissue growth factor (CTGF; or CCN2), which is known to contribute to GBM pathogenesis. Indeed, microRNA-18a (but not other miR-17∼92 members) has a functional site in the CTGF 3 ′ UTR, and its forced reexpression sharply reduces CTGF protein and mRNA levels. Interestingly, it also reduces the levels of CTGF primary transcript. The unexpected effects of miR-18a on CTGF transcription are mediated in part by direct targeting of Smad3 and ensuing weakening of TGFβ signaling. Having defined the TGFβ signature in GBM cells, we demonstrate a significant anti-correlation between miR-18 and TGFβ signaling in primary GBM samples from The Cancer Genome Atlas. Most importantly, high levels of miR-18 combined with low levels of the TGFβ metagene correlate with prolonged patient survival. Thus, low expression of the miR-17∼92 cluster, and specifically miR-18a, could significantly contribute to GBM pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Targeting of TGFβ signature and its essential component CTGF by miR-18 correlates with improved survival in glioblastoma

Fox

Dews

Minn

et al. 2012

RNA

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“…CTGF has been reported to confer the ability of drug resistance on tumor cells [19]. Clinically, IFN-gamma has the antitumor effects on treating thyroid cancer [20].…”

Section: Ctgf Inhibited Both Basal Level and Drug-induced Cell Apoptosismentioning

confidence: 99%

CTGF is overexpressed in papillary thyroid carcinoma and promotes the growth of papillary thyroid cancer cells

et al. 2011

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Connective tissue growth factor (CTGF or CCN2), which belongs to the CCN family, is a secreted protein. It has been implicated in various biological processes, such as cell proliferation, migration, angiogenesis, and tumorigenesis. In this study, we found that CTGF expression level was elevated in primary papillary thyroid carcinoma (PTC) samples and correlated with clinical features, such as metastasis, tumor size, and clinical stage. Overexpression of CTGF in PTC cells accelerated their growth in liquid culture and soft agar as well as protecting PTC cells from apoptosis induced by IFN-gamma treatment. Downregulation of CTGF in PTC cells inhibits cell growth in liquid culture and soft agar and induces the activation of caspase pathway and sensitized PTC cells to apoptosis. Our data suggest that CTGF plays an important role in PTC progression by supporting tumor cell survival and drug resistance, and CTGF may be used as a potential tumor marker for PTC diagnosis.

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“…Consistently, increased levels of TAZ were associated with increased levels of CTGF and Survivin (Supplementary Figure 5c), known to be its target genes and to have an important role in tumorigenesis. 19,20 …”

Section: Characterization and Validation Of Breast Cancer Stem Cells mentioning

confidence: 99%

TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells

et al. 2014

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Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs is the only cell population endowed with metastatic potential. Gene-expression profile studies comparing metastagenic and non-metastagenic cells identified TAZ, a transducer of the Hippo pathway and biomechanical cues, as a central mediator of BCSCs metastatic ability involved in their chemoresistance and tumorigenic potential. Overexpression of TAZ in low-expressing dBCCs induced cell transformation and conferred tumorigenicity and migratory activity. Conversely, loss of TAZ in BCSCs severely impaired metastatic colonization and chemoresistance. In clinical data from 99 BC patients, high expression levels of TAZ were associated with shorter disease-free survival in multivariate analysis, thus indicating that TAZ may represent a novel independent negative prognostic factor. Overall, this study designates TAZ as a novel biomarker and a possible therapeutic target for BC.

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Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme

Cited by 49 publications

References 29 publications

Targeting of TGFβ signature and its essential component CTGF by miR-18 correlates with improved survival in glioblastoma

Targeting of TGFβ signature and its essential component CTGF by miR-18 correlates with improved survival in glioblastoma

CTGF is overexpressed in papillary thyroid carcinoma and promotes the growth of papillary thyroid cancer cells

TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells

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