PRL-3 facilitates angiogenesis and metastasis by increasing ERK phosphorylation and up-regulating the levels and activities of Rho-A/C in lung cancer

Ming, Jian; Liu, Nan; Gu, Yumei; Qiu, Xueshan; Wang, Enhua

doi:10.1080/00313020802579268

Cited by 64 publications

(74 citation statements)

References 24 publications

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“…For this reason, many studies have focused on PRL-3 in lung cancer. The Ming group has reported that PRL-3 is expressed in all 94 cases of primary lung cancer patients and highly expressed in 64 cases (68%) by in situ immunohistochemical staining (11). In addition, the expression level is significantly associated with advanced clinical stage, lymph node and distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Mean age of the patients is 66 (±9) and eight of them are stage III and they are all pathologically confirmed positive N2 nodes after surgery. It has been reported that PRLs especially PRL-3 expression was positively correlated with the advanced stage of lung cancer (11). Thus, we examined protein expression of other PRLs by Western blot analysis.…”

Section: Increased Expression Of Prl-2 Protein In Lung Cancermentioning

confidence: 94%

“…In one study, the level of PRL-3 expression was decreased in metastatic primary lung cancer (10), while that of PRL-3 expression was positively correlated with the advanced stage of lung cancer in another study (11). Because of the controversies in primary lung cancer, we investigated the expression patterns and levels of PRL-1, -2 and -3 in primary lung cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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Altered expression of phosphatase of regenerating liver gene family in non-small cell lung cancer

Lee

2011

Oncol Rep

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Abstract. Protein tyrosine phophatases (PTPs) are implicated in the tumorigenesis and metastasis of human cancer. The phosphatase of regenerating liver (PRL) gene family, a subgroup of PTPs is also linked to these processes. In many solid cancers, high levels of PRL-3 expression are related with metastasis and poor prognosis. However, the expression patterns of PRL-1 and -2 have not been explored in lung cancer yet. Thus, we investigated the expression levels of PRL-1, -2 and -3 in the tissues of primary lung cancer patients. The protein expression levels of PRL-2, but not PRL-1 and -3 were increased in cancer tissues. However, there was no correlation between mRNA and protein expression levels of the PRLs. Reporter assays showed that PRLs suppressed the activity of the p21 promoter but promoted AP-1 activity. Furthermore, transfection of PRLs showed significantly increased cell proliferation. Therefore, these results suggest that PRL-2 plays an important role in lung cancer and can be a biomarker of lung cancer, substituting for the function of other PRLs.

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Section: Discussionmentioning

confidence: 99%

Section: Increased Expression Of Prl-2 Protein In Lung Cancermentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Altered expression of phosphatase of regenerating liver gene family in non-small cell lung cancer

Lee

2011

Oncol Rep

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“…Abnormal activation of the ERKs cascade is associated with metastasis in many human cancers. [15][16][17] Furthermore, we have shown that activation of ERK/AP-1 is associated with increased matrix metalloproteinases (MMPs) expression when pancreatic cancer cells are activated by IL-13 through IL-13Ra2. 12 To confirm a role of IL-13Ra2 in cancer invasion and metastasis, we have studied ovarian cancer, as metastasis in this cancer is correlated with prognosis of patients.…”

mentioning

confidence: 99%

IL‐13 regulates cancer invasion and metastasis through IL‐13Rα2 via ERK/AP‐1 pathway in mouse model of human ovarian cancer

Fujisawa

Joshi

Puri

2011

Intl Journal of Cancer

127

112

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Previously, we have demonstrated that a variety of human cancers including the ovarian cancer express IL-13Ra2, a high affinity receptor for IL-13. Herein, we have examined if IL-13 regulates invasion and metastasis of ovarian cancer through IL-13Ra2 in vitro and in vivo in animal models of human ovarian cancer. We tested cell invasion and protease activity in IL-13Ra2-overexpressing and IL-13Ra2-negative ovarian tumor cell lines. IL-13 treatment significantly augmented both cell invasion and enzyme activities in only IL-13Ra2-positive cells but not in IL-13Ra2-negative cells in vitro. Mechanistically, IL-13 enhanced ERK1/2, AP-1 and MMP activities only in IL-13Ra2-positive cells but not in IL-13Ra2-negative cells. In contrast, other signaling pathways such as IRS1/2, PI3K and AKT do not seem to be involved in IL-13 induced signaling in ovarian cancer cell lines. Highly specific inhibitors for MMP and AP-1 efficiently inhibited both invasion and protease activities without impacting the basal level invasion and protease activities in vitro. In orthotopic animal model of human ovarian cancer, IL-13Ra2-positive tumors metastasized to lymph nodes and peritoneum earlier than IL-13Ra2-negative tumors. Interestingly, the IL-13Ra2-positive tumor bearing mice died earlier than mice with IL-13Ra2-negative tumor. Intraperitoneal injection of IL-13 further shortened survival of IL-13Ra2-positive tumor bearing mice compared to IL-13Ra2-negative tumor mice. IL-13Ra2-positive tumors and lymph node metastasis expressed higher levels of MMPs and higher ERK1/2 activation compared to IL-13Ra2-negative tumors. Taken together, IL-13Ra2 is involved in cancer metastasis through activation of ERK/AP-1 and that targeting IL-13Ra2 might not only directly kill primary tumors but also prevent cancer metastasis.Ovarian cancer is the fifth major cause of cancer related deaths in women. It is estimated that 21,880 women will be diagnosed and 13,850 will die of ovarian cancer in 2010. 1 Severity of the disease is determined by staging, which is based on the distance and extent of cancer spread within the pelvic and peritoneal cavity. The 5-year survival rate of ovarian cancer patients is related to the stage of the disease. 2 Therefore, novel and effective anticancer therapies are needed to prevent cancer cell spread. We have previously reported that IL13Ra2 is a biomarker of disease in ovarian cancer and targeting of this receptor with specific immunotoxin decreases tumor burden and extends survival of animals. 3 Despite its overexpression in a variety of human tumors and its characterization as a potent target for receptor directed anticancer therapy, 4-7 the biology of this receptor is highly complex and not understood completely. IL-13Ra2 is one of two receptor subunits of IL-13R complex. Another key-player of the receptor complex is IL-13Ra1, which forms a productive complex with IL-4Ra upon binding to IL-13 and mediates signal transduction. On the other hand, IL13Ra2 does not seem to require IL-4Ra and by itself binds IL-13 with high af...

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“…Furthermore, poor patient prognosis and increased tumor invasiveness are commonly observed in many different malignancies expressing high levels of PTP4A3 (4,5). Although the specific PTP4A substrates have remained elusive, several downstream signaling pathways have been proposed including: PI3K/AKT (6), Src (7), ERK1/2 (8), and Rho GTPases (9). Considering the multitude of proposed signaling effectors, it is likely that the function of PTP4A3 is tightly regulated by cell type and specific cues from the extracellular environment.…”

mentioning

confidence: 99%

Protein-tyrosine Phosphatase 4A3 (PTP4A3) Promotes Vascular Endothelial Growth Factor Signaling and Enables Endothelial Cell Motility

Zimmerman

McQueeney

Isenberg

et al. 2014

Journal of Biological Chemistry

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PRL-3 facilitates angiogenesis and metastasis by increasing ERK phosphorylation and up-regulating the levels and activities of Rho-A/C in lung cancer

Cited by 64 publications

References 24 publications

Altered expression of phosphatase of regenerating liver gene family in non-small cell lung cancer

Altered expression of phosphatase of regenerating liver gene family in non-small cell lung cancer

IL‐13 regulates cancer invasion and metastasis through IL‐13Rα2 via ERK/AP‐1 pathway in mouse model of human ovarian cancer

Protein-tyrosine Phosphatase 4A3 (PTP4A3) Promotes Vascular Endothelial Growth Factor Signaling and Enables Endothelial Cell Motility

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