Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ROR1 is a conserved oncoembryonic surface protein expressed in breast cancer. Here we report that ROR1 associates with cortactin in primary breast-cancer cells or in MCF7 transfected to express ROR1. Wnt5a also induced ROR1-dependent tyrosine phosphorylation of cortactin (Y421), which recruited ARHGEF1 to activate RhoA and promote breast-cancer-cell migration; such effects could be inhibited by cirmtuzumab, a humanized mAb specific for ROR1. Furthermore, treatment of mice bearing breast-cancer xenograft with cirmtuzumab inhibited cortactin phosphorylation in vivo and impaired metastatic development. We established that the proline at 841 of ROR1 was required for it to recruit cortactin and ARHGEF1, activate RhoA, and enhance breast-cancer-cell migration in vitro or development of metastases in vivo. Collectively, these studies demonstrate that the interaction of ROR1 with cortactin plays an important role in breast-cancer-cell migration and metastasis.
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PMID:Wnt5a induces ROR1 to recruit cortactin to promote breast-cancer migration and metastasis. 3166 37

Tumor metastasis is one of death causes for patients of prostate carcinoma. PIWI-interacting RNAs (piRNAs) are a subtype of noncoding protein RNAs that are involved in tumorigenesis, but the effect of piRNAs in prostate carcinoma (PCa) remains unclear. This article showed the identification of piRNAs was performed using a piRNA microarray screen in PCa tissues and several piRNAs were identified as dysregulated. The two up-regulated piRNAs (piR-19004 and piR-2878) and one down-regulated piR-19166 have been validated in the tissues and cell lines of PCa using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Further studies showed that piR-19166 is transfected into PCa cells to suppress its migration and metastasis. Mechanistically, cortactin (CTTN) 3' untranslated region (UTR) was complementary combined with piR-19166 by bioinformatic prediction and identified as a direct target of piR-19166 through dual-luciferase reporter assay. Over-expression and knockdown of CTTN could respectively rescue and simulate the effects induced by piR-19166. Finally, piR-19166 suppresses migration and metastasis by the CTTN/matrix metalloproteinases (MMPs) pathway in PCa cells. Thus, these findings suggested that piR-19166 targets the CTTN of prostate cancer cells to inhibit migration and distant metastasis, and may represent a new marker of diagnosis and treatment for PCa patients in early stages.
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PMID:piR-19166 inhibits migration and metastasis through CTTN/MMPs pathway in prostate carcinoma. 3288 13

Metastasis is a major cause of death in patients with colorectal cancer (CRC). Cysteine-rich protein 2 (CSRP2) has been recently implicated in the progression and metastasis of a variety of cancers. However, the biological functions and underlying mechanisms of CSRP2 in the regulation of CRC progression are largely unknown. Methods: Immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were used to detect the expression of CSRP2 in CRC tissues and paracancerous tissues. CSRP2 function in CRC was determined by a series of functional tests in vivo and in vitro. WB and immunofluorescence were used to determine the relation between CSRP2 and epithelial-mesenchymal transition (EMT). Co-immunoprecipitation and scanning electron microscopy were used to study the molecular mechanism of CSRP2 in CRC. Results: The CSRP2 expression level in CRC tissues was lower than in adjacent normal tissues and indicated poor prognosis in CRC patients. Functionally, CSRP2 could suppress the proliferation, migration, and invasion of CRC cells in vitro and inhibit CRC tumorigenesis and metastasis in vivo. Mechanistic investigations revealed a physical interaction between CSRP2 and p130Cas. CSRP2 could inhibit the activation of Rac1 by preventing the phosphorylation of p130Cas, thus activating the Hippo signaling pathway, and simultaneously inhibiting the ERK and PAK/LIMK/cortactin signaling pathways, thereby inhibiting the EMT and metastasis of CRC. Rescue experiments showed that blocking the p130Cas and Rac1 activation could inhibit EMT induced by CSRP2 silencing. Conclusion: Our results suggest that the CSRP2/p130Cas/Rac1 axis can inhibit CRC aggressiveness and metastasis through the Hippo, ERK, and PAK signaling pathways. Therefore, CSRP2 may be a potential therapeutic target for CRC.
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PMID:CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways. 3304 70


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