PBX3 promotes migration and invasion of colorectal cancer cells<i>via</i>activation of MAPK/ERK signaling pathway

Han, H.; Gu, Jin; Ji, Deng Bo; Li, Zhao Wei; Zhang, Yuan; Zhao, Wei; Wang, Li Min; Zhang, Zhi‐Qian

doi:10.3748/wjg.v20.i48.18260

Cited by 62 publications

(66 citation statements)

References 26 publications

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“…In recent years there have been a handful of publications addressing the role of PBX3 as a prognostic marker. In colorectal cancer, high levels of PBX3 mRNA have been associated with decreased overall survival time after surgery . In gastric cancer tissue, PBX3 was mainly detected in the nucleus of carcinoma cells and was positively correlated with local invasion, clinical stage and tumor grade …”

Section: Discussionmentioning

confidence: 99%

PBX3 is a putative biomarker of aggressive prostate cancer

Ramberg

Grytli

Nygård

et al. 2016

Intl Journal of Cancer

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There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081-0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46-0.93, p values < 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer.

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Section: Discussionmentioning

confidence: 99%

PBX3 is a putative biomarker of aggressive prostate cancer

Ramberg

Grytli

Nygård

et al. 2016

Intl Journal of Cancer

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“…For depletion of endogenous PBX3 expression, short hairpin RNA (shRNA) targeting 592–613 bp was inserted into a lentivirus vector as previously described (6). Lentiviral vectors were then transfected into MKN-45 GC cells.…”

Section: Methodsmentioning

confidence: 99%

“…In colorectal cancer, let-7c serves as a tumor metastasis suppressor by inhibiting PBX3 expression (13), and PBX3 expression is significantly associated with lymph node invasion, distant metastasis and poor overall survival. PBX3 can stimulate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase signaling pathway in colorectal cancer (6). Additionally, the forced expression of PBX3 may reverse the effects caused by microRNA-181b that promote apoptosis, inhibit proliferation and delay leukemogenesis in cytogenetically abnormal acute myeloid leukemia (14).…”

Section: Introductionmentioning

confidence: 99%

PBX3 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition

Wang

et al. 2016

Oncology Letters

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The overexpression of pre-leukemia transcription factor 3 (PBX3) in tumors plays an important role in invasion, metastasis and proliferation in a variety of human cancer types. Tumor metastasis and angiogenesis significantly contribute to the progression of cancer and create challenges for cancer therapy. In the present study, reverse transcription-polymerase chain reaction demonstrated that PBX3 was upregulated in gastric cancer (GC) tissues and Transwell assay revealed that the overexpression of PBX3 promoted GC invasion and metastasis in vitro. In addition, a nude mouse xenograft model was established, which demonstrated that PBX3 promoted peritoneal metastases in vivo. Furthermore, the overexpression of PBX3 in GC promoted the tubular formation of human umbilical vein endothelial cells. Western blot analysis revealed that overexpressed PBX3 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT protein markers N-cadherin and vimentin, while E-cadherin expression was reduced in PBX3-overexpressing GC cells. Contrasting results were observed in PBX3-knockdown GC cells. Additionally, the overexpression of PBX3 increased the levels of phosphorylated AKT (Ser473), which is involved in the progression of a variety of human cancers. Gelatin zymography assay demonstrated that the overexpression of PBX3 also elevated matrix metalloproteinase-9 activity in GC, which was closely associated with tumor metastasis and angiogenesis. Based on these findings, it may be concluded that PBX3 enhances invasion and metastasis in GC by promoting EMT, possibly via the AKT signaling pathway.

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“…It has been found to be down regulated in breast, colorectal tumours, hepatocellular carcinomas (13) and multiple myeloma (18). So far two targets genes have been identified: cMyc, whose role as oncogene needs no introduction and PBX3 (19) which belong to the Pre-B-cell leukemia homeobox family PBX. PBX3 is downstream to, and is activated by, the ERK1/ERK2 complex in the MAPK pathway (19).…”

Section: Exosomes and The Tsg Mirna-230amentioning

confidence: 99%

“…So far two targets genes have been identified: cMyc, whose role as oncogene needs no introduction and PBX3 (19) which belong to the Pre-B-cell leukemia homeobox family PBX. PBX3 is downstream to, and is activated by, the ERK1/ERK2 complex in the MAPK pathway (19).…”

Section: Exosomes and The Tsg Mirna-230amentioning

confidence: 99%