The Matricellular Protein CCN1/Cyr61 Is a Critical Regulator of Sonic Hedgehog in Pancreatic Carcinogenesis

Haque, Inamul; De, Archana; Majumder, Monami; Mehta, Smita; McGregor, Douglas H.; Banerjee, Sushanta K.; Veldhuizen, Peter J. Van; Banerjee, Snigdha

doi:10.1074/jbc.m112.389064

Cited by 48 publications

(48 citation statements)

References 55 publications

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“…This finding strongly corroborates our findings that CCN1 and CCN3 activate Notch-1 signaling and thereby reduce proliferation of the cytotrophoblast cell line SGHPL-5, as reported by Haider et al 41 CCN proteins are known to act via Notch-1 in other systems, such as myoblasts. [42][43][44][45] Our recent studies showed that Notch/p21 signaling also seems to mediate the proliferation-reducing activity of CCN3 in malignant Jeg3 cells. 14 In the present study we found that CCN1 and CCN3 cause a G0/G1 cell cycle arrest and induce cellular senescence in SGHPL-5 trophoblast cells; this effect is presumably mediated by activation of the Notch-1 receptor after upregulation of p21.…”

Section: Discussionmentioning

confidence: 99%

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

Kipkeew

Kirsch

Klein

et al. 2016

Cell Adhesion & Migration

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Section: Discussionmentioning

confidence: 99%

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

Kipkeew

Kirsch

Klein

et al. 2016

Cell Adhesion & Migration

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“…Coupled with the ability of CCN1 and CCN2 to mediate proangiogenesis in cancer (Chintalapudi et al 2008), and CCN1 for αVβ5 mediated cancer cell migration (Jandova et al 2012), we have here a scenario of facilitated tumor cell invasion. Haque et al (2012) reported that CCN1 is a critical regulator of sonic hedgehog in pancreatic carcinogenesis. Working with pancreatic cancer cell lines they showed that CCN1 silencing interfered with Shh downstream signaling and inhibition of Notch1 degradation thus sustaining the proliferative drive.…”

Section: Ccn Proteins and Cancermentioning

confidence: 99%

CCN family of proteins: critical modulators of the tumor cell microenvironment

Yeger

Perbal

2016

J. Cell Commun. Signal.

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The CCN family of proteins consisting of CCN1 (Cyr61), CCN2 (CTGF), CCN3 (NOV), CCN4 (WISP-1), CCN5 (WISP-2) and CCN6 (WISP-3) are considered matricellular proteins operating essentially in the extracellular microenvironment between cells. Evidence has also been gradually building since their first discovery of additional intracellular roles although the major activity is triggered at the cell membrane. The proteins consist of 4 motifs, a signal peptide (for secretion} followed consecutively by the IGFBP, VWC, TSP1 and CT (C-terminal cysteine knot domain) motifs, which signify their potential binding partners and functional connections to a variety of key regulators of physiological processes. With respect to cancer it is now clear that, whereas certain members can facilitate tumor behavior and progression, others can competitively counter the process. It is therefore clear that the net outcome of biological interactions in the matrix and what gets signaled or inhibited can be a function of the interplay of these CCN 1-6 proteins. Because the CCN proteins further interact with other key proteins, like growth factors in the matrix, the balance is not only important but can vary dynamically with the physiological states of tumor cells and the surrounding normal cells. The tumor niche with its many cell players has surfaced as a critical determinant of tumor behavior, invasiveness, and metastasis. It is in this context that CCN proteins should be investigated with the potential of being recognized and validated for future therapeutic approaches.

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“…[19][20][21] Briefly, 50 μg total protein was separated by SDS-PAGE and transferred to nitrocellulose membrane (Trans-blot transfer medium, Bio-Rad). The membranes were probed with primary antibodies for a specified period of time as per the manufacturer's instructions.…”

Section: Western Blot Analysismentioning

confidence: 99%

Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition

Maity

Das

et al. 2015

Laboratory Investigation

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Acetylsalicylic acid (ASA), also known as aspirin, a classic, nonsteroidal, anti-inflammatory drug (NSAID), is widely used to relieve minor aches and pains and to reduce fever. Epidemiological studies and other experimental studies suggest that ASA use reduces the risk of different cancers including breast cancer (BC) and may be used as a chemopreventive agent against BC and other cancers. These studies have raised the tempting possibility that ASA could serve as a preventive medicine for BC. However, lack of in-depth knowledge of the mechanism of action of ASA reshapes the debate of risk and benefit of using ASA in prevention of BC. Our studies, using in vitro and in vivo tumor xenograft models, show a strong beneficial effect of ASA in the prevention of breast carcinogenesis. We find that ASA not only prevents breast tumor cell growth in vitro and tumor growth in nude mice xenograft model through the induction of apoptosis, but also significantly reduces the self-renewal capacity and growth of breast tumor-initiating cells (BTICs)/breast cancer stem cells (BCSCs) and delays the formation of a palpable tumor. Moreover, ASA regulates other pathophysiological events in breast carcinogenesis, such as reprogramming the mesenchymal to epithelial transition (MET) and delaying in vitro migration in BC cells. The tumor growth-inhibitory and reprogramming roles of ASA could be mediated through inhibition of TGF-β/ SMAD4 signaling pathway that is associated with growth, motility, invasion, and metastasis in advanced BCs. Collectively, ASA has a therapeutic or preventive potential by attacking possible target such as TGF-β in breast carcinogenesis.

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The Matricellular Protein CCN1/Cyr61 Is a Critical Regulator of Sonic Hedgehog in Pancreatic Carcinogenesis

Cited by 48 publications

References 55 publications

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

CCN family of proteins: critical modulators of the tumor cell microenvironment

Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition

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