PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell

Wang, Xiaoxia; Qian, Cheng; Zhang, Shang-Nuan; Qian, Heya; Wu, Jinxia; Tian, Hui; Pei, Dong‐Sheng; Zheng, Junnian

doi:10.1007/s13277-013-0824-x

Cited by 48 publications

(37 citation statements)

References 35 publications

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“…However, the overexpression of PAK7 increases the migration and invasion of colon cancer cells in vitro . Our findings are consistent with other recent studies, which have identified an important role of PAK7 in tumorigenesis and metastasis of breast, pancreatic, and gastric cancer cells [21, 27, 28]. …”

Section: Discussionsupporting

confidence: 94%

High-level expression of P21-Cdc/Rac-activated kinase 7 is closely related to metastatic potential and poor prognosis of colon carcinoma

Chen

Wang

et al. 2016

Oncotarget

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P21 protein (Cdc42/Rac)-activated kinase 7 (PAK7) can promote neurite outgrowth, induce microtubule stabilization, and activate cell survival signaling pathways. PAK7 expression was found to increase with colon carcinoma progression, but the prognostic value, clinical significance, and underlying mechanisms have not been explored. In my study, the expression of PAK7 was up-related at both the transcriptional and the translational levels in colon tumors compared to that in adjacent normal colon tissue. Patients with PAK7-positive tumors had a lower rate of overall survival (OS) and metastasis-free survival (MFS) (log-rank test, P < 0.001). A Cox proportional hazards model showed that PAK7 expression was an independent prognostic factor for OS (hazard ration [HR], 2.08; 95% confidence interval [CI], 1.16-3.73; P = 0.004) and MFS (HR, 2.88; 95% CI, 1.53-5.42; P < 0.001) in patients with colon cancer. Patients with tumors that were over-expressing PAK7 experienced metastasis, and died within a significantly shorter time after surgery (P < 0.001). Knockdown of PAK7 by a specific short hairpin RNA (shRNA) significantly suppressed the progression of epithelial to mesechymal transition (EMT), migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. However, overexpression of PAK7 significantly promoted these processes. These findings indicate that aberrant PAK7 expression is associated with the occurrence of metastasis and poor clinical outcomes of human colon cancer by promoting the EMT, and the assessment of PAK7 expression might be helpful in predicting metastasis and prognostication for patients with colon cancer.

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Section: Discussionsupporting

confidence: 94%

High-level expression of P21-Cdc/Rac-activated kinase 7 is closely related to metastatic potential and poor prognosis of colon carcinoma

Chen

Wang

et al. 2016

Oncotarget

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“…In the network presented herein, miR-9 directly targeted HMGA2, EGR1 and IGFBP3. These three coding RNAs are closely related to the invasion and metastasis of breast cancer [20, 26, 27]. The expression level of miR-210 in MDA-MB-231 cells is 4 times higher than that in MCF-7 cells in the present study.…”

Section: Discussionmentioning

confidence: 45%

Differential Expression Profiles of the Transcriptome in Breast Cancer Cell Lines Revealed by Next Generation Sequencing

Shi

Peng

Long³

2017

Cell Physiol Biochem

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Background/Aims: As MCF-7 and MDA-MB-231 cells are the typical cell lines of two clinical breast tumour subtypes, the aim of the present study was to elucidate the transcriptome differences between MCF-7 and MDA-MB-231 breast cancer cell lines. Methods: The mRNA, miRNA (MicroRNA) and lncRNA (Long non-coding RNA) expression profiles were examined using NGS (next generation sequencing) instrument Illumina HiSeq-2500. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses were performed to identify the biological functions of differentially expressed coding RNAs. Subsequently, we constructed an mRNA-ncRNA (non-coding RNA) targeting regulatory network. Finally, we performed RT-qPCR (real-time quantitative PCR) to confirm the NGS results. Results: There are sharp distinctions of the coding and non-coding RNA profiles between MCF-7 and MDA-MB-231 cell lines. Among the mRNAs and ncRNAs with the most differential expression, SLPI, SOD2, miR-7, miR-143 and miR-145 were highly expressed in MCF-7 cells, while CD55, KRT17, miR-21, miR-10b, miR-9, NEAT1 and PICSAR were over-expressed in MDA-MB-231 cells. Differentially expressed mRNAs are primarily involved in biological processes of locomotion, biological adhesion, ECM-receptor interaction pathway and focal adhesion. In the targeting regulatory network of differentially expressed RNAs, mRNAs and miRNAs are primarily associated with tumour metastasis, but the functions of lncRNAs remain uncharacterized. Conclusion: These results provide a basis for future studies of breast cancer metastasis and drug resistance.

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“…Genetic experiments suggest that Pak mediates certain aspects of extracellular matrix organization downstream of CDC42, as matrix remodeling could not be restored to Cdc42 −/ − MEFs by reintroducing mutants of CDC42 that lacked Pak binding 60 . PAK1, 2, 4, and 5 have been shown to regulate MMP expression in a variety of cancer cell types 61, 626364 . Increased expression of MMPs has been suggested to result from Pak-mediated activation of JUN N-terminal kinase (JNK) 65, 66 .…”

Section: Activating Invasion and Metastasismentioning

confidence: 99%

PAK signalling during the development and progression of cancer

et al. 2013

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p21-activated kinases (Paks) are positioned at the nexus of several oncogenic signaling pathways. Overexpression or mutational activation of Pak isoforms is frequently seen in various human tumors, and recent data suggests that excessive Pak activity drives many cellular processes that are the hallmarks of cancer. In this review, we discuss the mechanisms of Pak activation in cancer, the key substrates for this family of kinases that mediate their developmental and oncogenic effects, and how small molecule inhibitors of these enzymes might best be developed and deployed in the treatment of cancer.

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PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell

Cited by 48 publications

References 35 publications

High-level expression of P21-Cdc/Rac-activated kinase 7 is closely related to metastatic potential and poor prognosis of colon carcinoma

High-level expression of P21-Cdc/Rac-activated kinase 7 is closely related to metastatic potential and poor prognosis of colon carcinoma

Differential Expression Profiles of the Transcriptome in Breast Cancer Cell Lines Revealed by Next Generation Sequencing

PAK signalling during the development and progression of cancer

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