ERK1/2 Regulation of CD44 Modulates Oral Cancer Aggressiveness

Judd, Nancy P.; Winkler, Ashley E.; Murillo, Oihana; Brotman, Joshua J.; Law, Jonathan H.; Lewis, James S.; Dunn, Gavin P.; Bui, Jack D.; Sunwoo, John B.; Uppaluri, Ravindra

doi:10.1158/0008-5472.can-11-1831

Cited by 182 publications

(181 citation statements)

References 48 publications

Supporting

Mentioning

162

Contrasting

Order By: Relevance

“…It was also shown in the same study that knockdown of CD44v6 by siRNA decreased prostate cancer cell invasive and adhesive ability to hyaluronic acid (HA), suggesting that CD44v6 is an important participant in mediating tumor cell adhesion during metastasis (3). Another study showed that CD44 was a downstream effector of ERK1/2 inducing cell migration and invasion in vitro and tumor growth and metastasis in vivo in human oral cancer (19). It was reported that CD44v6 induced EMT in prostate cancer and the induction of EMT was accompanied by a shift in CD44 isoforms in breast cancer cells (49).…”

Section: Discussionmentioning

confidence: 98%

Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells

et al. 2015

View full text Add to dashboard Cite

Abstract. Advanced prostate cancer has highly invasive potential, which may lead to metastasis associated with poor prognosis. Sulforaphane (SFN), abundant in cruciferous vegetables, exhibited effective resistance to carcinogenesis in a variety of tumors. The aim of the present study was to investigate whether SFN inhibited invasion in human prostate cancer cells via sustained activation of ERK1/2 and downstream signaling by an invasion assay, gelatin zymography and western blot analysis. The results showed that SFN inhibited invasion and we characterized the underlying mechanisms in human DU145 prostate cancer cells. SFN (15 µM) changed cell morphology leading to short-cell pseudopodia which may suppress tumor migration and invasion. The Transwell assay showed that SFN phosphorylated ERK1/2 in a doseand time-dependent manner and significantly inhibited cell invasion, while the effect was reduced by the ERK1/2 blocker PD98059 (25 µM). Furthermore, these effects contributed to the upregulation of E-cadherin and the downregulation of CD44v6 and were eradicated by PD98059. Western blot analysis and gelatin zymography showed that SFN decreased the expression and activity of MMP-2. Thus, SFN inhibited invasion by activating ERK1/2 to upregulate E-cadherin and downregulate CD44v6, thereby reducing MMP-2 expression and activity. E-cadherin is an invasion inhibitor, while CD44v6 and MMP-2 are invasion promoters. Therefore, SFN is a prospective therapeutic agent that may be used to prevent invasion in prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 98%

Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Similarly, Wang et al indicated that overexpression of activated Erk1/2 and cyclin D1 proteins are involved in oral tongue carcinogenesis (51). Finally, Judd et al (59) reported that MEK1 activation enhances CD44 expression and promotes aggressiveness in HNSCC, while Katada et al (60) and Zuo et al (61) suggested that Erk1/2 activation correlates with increased cell migration and invasion in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

et al. 2014

View full text Add to dashboard Cite

Abstract. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway possesses confirmed oncogenic potential in oral squamous cell carcinoma (OSCC). Crosstalk with other molecular pathways contributes to STAT3 regulation in cancer. The effects of mitogen-activated protein kinases (MAPKs) and particularly extracellular signal-regulated kinase 1/2 (Erk1/2) on STAT3 signaling in OSCC have not been thoroughly investigated. The present study examined the effects of Erk1/2 modulation on STAT3 signaling and cell growth in OSCC cells. Constitutive expression levels of phosphorylated (tyrosine and serine) and total STAT3, Erk1/2 and cyclin D1 were assessed in OSCC cell lines. Erk1/2 modulation was achieved by pharmacological agents; siRNA silencing against Erk1/2 was also performed. Cell proliferation and viability were assessed. Erk1/2 inhibition with either U0126 treatment or specific siRNA silencing resulted in decreases in p-ser STAT3 and cyclin D1 levels and increases in p-tyr STAT3 in OSCC cells. Moreover, Erk1/2 inhibition resulted in a dose-dependent reduction in OSCC cell growth and viability. Erk1/2 induction had the opposite effects. Taken together, these results are supportive of an active crosstalk between the oncogenic Erk1/2 and STAT3 pathways in OSCC, the significance of which requires further investigation.

show abstract

“…MAPK/ERK, one classic downstream signal of the EGFR pathway, could regulate CD44 to modulate tumor aggressiveness (38). The most recent study showed that prostate cancer cell migration and invasion were inhibited by reducing MMP-2/-9 expression via the ROS/ERK pathways (39).…”

Section: Discussionmentioning

confidence: 99%

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

2015

View full text Add to dashboard Cite

Abstract. Asporin (ASPN), a novel member of the small leucine-rich proteoglycan (SLRP) family, serves as a key component of the tumor stroma and has been reported to be abnormally expressed in certain types of tumors. Specifically, the proteoglycan was proven to activate the coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. However, the role of ASPN in cancer cell growth and metastasis has not yet been addressed. In the present study, we aimed to evaluate the tumoricidal benefits of ASPN on tumorigenesis and progression of gastric cancer. Firstly, it was demonstrated that ASPN was overexpressed in gastric carcinoma tissues when compared to the corresponding non-cancerous tissues, and it had varied levels of expression in gastric cancer epithelial cell lines. Additionally, we assessed the effects of transient siRNA-mediated ASPN knockdown on gastric cancer cells. ASPN silencing inhibited proliferation and suppressed the migration of immortalized neoplastic epithelial cells. Furthermore, at the molecular level, we found that downregulation of ASPN blocked the anti-apoptotic molecule Bcl-2, increased the expression of pro-apoptotic molecule Bad, reduced the expression of migration-related proteins CD44 and matrix metalloproteinase (MMP)-2, and abrogated the activation of the phosphorylation status of ERK and epidermal growth factor (EGF) and its receptor (EGFR). Collectively, our findings indicate that ASPN is upregulated and plays an oncogenic role in gastric cancer progression and metastasis by influencing the EGFR signaling pathway.

show abstract

ERK1/2 Regulation of CD44 Modulates Oral Cancer Aggressiveness

Cited by 182 publications

References 48 publications

Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells

Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

Contact Info

Product

Resources

About