Elevation of intracellular cyclic AMP inhibits NF-κB-mediated thymosin β4 expression in melanoma cells

Kim, Aeyung; Son, Min-Sik; Kim, Keun Il; Yang, Young; Song, Eun Young; Lee, Hee Gu; Lim, Jong‐Seok

doi:10.1016/j.yexcr.2009.05.024

Cited by 23 publications

(19 citation statements)

References 42 publications

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“…In addition, we found that Tβ4 overexpression induced an EMT-like phenotype in OSCCs accompanied by downregulation of E-cadherin and upregulation of mesenchymal molecular markers such as N-cadherin and vimentin, which are known to induce EMT (Thiery and Sleeman 2006). Also, we observed that Tβ4-overexpressing OSCCs showed an elongated, scattered, and fibroblastic morphology compared to the cobblestone-like morphology of the vector-control cells (Wang et al 2012;Kim et al 2009;Huang et al 2007a).…”

Section: Discussionmentioning

confidence: 63%

Thymosin β4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma

et al. 2015

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The epithelial-to-mesenchymal transition (EMT) plays a vital role in carcinogenesis, invasion, and metastasis of many epithelial tumors including oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck. However, the functional role of the actin-sequestering protein thymosin β4 (Tβ4) in the EMT in OSCCs remains unclear. Thus, we investigated whether overexpression of Tβ4 could induce in vitro tumorigenesis such as cell proliferation and anchorage independency and an EMT-like phenotype in OSCCs. Also, we examined whether it affects invasiveness and cell motility-associated signaling molecules. Tβ4-overexpressing OSCCs, SCC-15_Tβ4 and SCC-25_Tβ4, enhanced cell proliferation and colony formation. In addition, we observed that Tβ4 overexpression induced an EMT-like phenotype, accompanied by a decrease in expression of the epithelial cell marker E-cadherin and an increase in expression of mesenchymal cell markers vimentin and N-cadherin. Also, the expression level of Twist1, an EMT-inducing transcription factor, was significantly enhanced in SCC-15_Tβ4 and SCC-25_Tβ4 cells. Tβ4 overexpression augmented in vitro invasion and MMP-2 activity and enhanced the phosphorylation of paxillin and cortactin and expression of LIMK1. Taken together, these results suggest that Tβ4 overexpression could be one of the causes of tumorigenesis and progression in OSCCs. Further investigation on the Tβ4 molecule would encourage the development of specific targets for cancer treatment.

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Section: Discussionmentioning

confidence: 63%

Thymosin β4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma

et al. 2015

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“…Our finding reveals that E-cadherin protein level is upregulated, whereas vimentin and a-SMA are downregulated in Ad-POMC-treated melanoma cells and lung colonies. Microarray analysis unveiled that POMC is a potent antimetastatic suppressor by simultaneous repression of multiple prometastatic genes such as fibronectin, CTGF (42,43), Tb4 (27,44), and HDGF (45). Our recent study showed that HDGF upregulation is correlated with recurrence, lymph node metastasis, and EMT in patients with breast cancer (15).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, POMC-derived peptide, a-MSH, has been reported to trigger melanoma/melanocyte differentiation (23,24) and potently inhibits both the in vitro and in vivo invasion of highly invasive B16-BL6 melanoma cells (25,26). A recent study has indicated that prophylactic a-MSH treatment decreased the metastatic potential of melanoma cells in vitro and in vivo (27). These findings suggested that peripheral POMC expression may inhibit invasive and metastasis.…”

Section: Introductionmentioning

confidence: 96%

Downregulation of Hepatoma-Derived Growth Factor Contributes to Retarded Lung Metastasis via Inhibition of Epithelial–Mesenchymal Transition by Systemic POMC Gene Delivery in Melanoma

Tsai

Liu

Kung

et al. 2013

Molecular Cancer Therapeutics

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The prognosis of malignant melanoma is poor due to high incidence of metastasis, underscoring the demand for development of novel therapeutic strategies. Stress hormone pro-opiomelanocortin (POMC) is the precursor for several anti-inflammatory peptides that hold promise for management of cancer-related diseases. The present study evaluated the antimetastatic potential and mechanism of POMC therapy for metastatic melanoma. Adenovirus-mediated POMC gene delivery potently inhibited the invasiveness of human and mouse melanoma cells. Moreover, after induction of lung metastasis, systemic POMC expression significantly reduced the foci formation and neovascularization in lungs. Mechanistic studies revealed that POMC therapy inhibited the epithelial-mesenchymal transition (EMT) of melanoma cells by upregulation of E-cadherin and downregulation of vimentin and a-smooth muscle actin (a-SMA). In addition, microarray analysis unveiled POMC gene transfer reduced the mRNA level of multiple prometastatic factors, including hepatoma-derived growth factor (HDGF). Cell culture and immunohistochemical studies further confirmed that POMC gene delivery significantly decreased the expression of HDGF in melanoma cells and tissues. Despite stimulating the invasion and EMT, exogenous HDGF supply only partially attenuated the POMC-mediated invasion inhibition and EMT change in melanoma cells. Finally, we delineated the contribution of melanocortins to POMC-induced inhibition of invasion, HDGF downregulation, and E-cadherin upregulation. Together, these results indicate that HDGF downregulation participates in POMC-induced suppression of metastasis and EMT in melanoma. Mol Cancer Ther; 12(6); 1016-25. Ó2013 AACR.

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“…[51,56,59,62,83,150,153,157,164,170] = [137,160,162] IL-12 - [131,137,147] TNF-a - [48,49,69,73,80,81,90,132,135,137,142,143,145,147,156,162,169] M-CSF - [45,166] G-CSF ? [90] GM-CSF - [160] IFN-b - [137] IL Thymosin b4 - [76] IgGj light chain ? [41,42] IL-1RA ?…”

Section: Effects Of Camp On Nf-jb Dimer Compositionmentioning

confidence: 99%

Cyclic AMP: a selective modulator of NF-κB action

Gerlo

Kooijman

Beck

et al. 2011

Cell. Mol. Life Sci.

160

142

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It has been known for several decades that cyclic AMP (cAMP), a prototypical second messenger, transducing the action of a variety of G-protein-coupled receptor ligands, has potent immunosuppressive and anti-inflammatory actions. These actions have been attributed in part to the ability of cAMP-induced signals to interfere with the function of the proinflammatory transcription factor Nuclear Factor-kappaB (NF-κB). NF-κB plays a crucial role in switching on the gene expression of a plethora of inflammatory and immune mediators, and as such is one of the master regulators of the immune response and a key target for anti-inflammatory drug design. A number of fundamental molecular mechanisms, contributing to the overall inhibitory actions of cAMP on NF-κB function, are well established. Paradoxically, recent reports indicate that cAMP, via its main effector, the protein kinase A (PKA), also promotes NF-κB activity. Indeed, cAMP actions appear to be highly cell type- and context-dependent. Importantly, several novel players in the cAMP/NF-κB connection, which selectively direct cAMP action, have been recently identified. These findings not only open up exciting new research avenues but also reveal novel opportunities for the design of more selective, NF-κB-targeting, anti-inflammatory drugs.

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Elevation of intracellular cyclic AMP inhibits NF-κB-mediated thymosin β4 expression in melanoma cells

Cited by 23 publications

References 42 publications

Thymosin β4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma

Thymosin β4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma

Downregulation of Hepatoma-Derived Growth Factor Contributes to Retarded Lung Metastasis via Inhibition of Epithelial–Mesenchymal Transition by Systemic POMC Gene Delivery in Melanoma

Cyclic AMP: a selective modulator of NF-κB action

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