Loss of profilin�2 contributes to enhanced epithelial-mesenchymal transition and metastasis of colorectal cancer

Zhang, Hui; Yang, Wenting; Yan, Jing; Zhou, Kaiping; Wan, Boshun; Shi, Peidong; Chen, Yueyu; He, Songbing; Li, Dechun

doi:10.3892/ijo.2018.4475

Cited by 18 publications

(17 citation statements)

References 37 publications

(39 reference statements)

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“…1B). PFN2 was reported to be involved in epithelial-to-mesenchymal transition (Tang et al 2015;Zhang et al 2018). Next, we detected PFN2 expression and found that PFN2 expression in glomerular endothelial cells was higher in DN patients than in control participants (Fig.…”

Section: Occurrence Of Endmt and Increase In Pfn2 Expression In Dn Patients And Ratsmentioning

confidence: 88%

“…2A-E). Previous research indicated that PFN2 participates in epithelialto-mesenchymal transition (Tang et al 2015;Zhang et al 2018). Therefore, PFN2 expression was detected in HUVECs.…”

Section: High-glucose Treatment Induced Endmt Via An Increase In Pfn2 Levels In Huvecsmentioning

confidence: 92%

“…Profilins are well known as actin-binding proteins (Ding et al 2012). Previous studies have indicated that profilin2 (PFN2) participates in epithelial-to-mesenchymal transition in cancer cells (Tang et al 2015;Zhang et al 2018). However, whether PFN2 participates in hyperglycemia-mediated EndMT in endothelial cells has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy

Zhong

et al. 2021

Mol Med

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Background Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. The endothelial-to-mesenchymal transition (EndMT) of glomerular endothelial cells has been reported to play a crucial role in DN. As a specific form of epithelial-to-mesenchymal transition, EndMT and epithelial-to-mesenchymal transition may exhibit mutual modulators. Profilin 2 (PFN2) has been reported to participate in epithelial-to-mesenchymal transition. Moreover, ETS proto-oncogene 1 (ets1) and lysine methyltransferase 5A (KMT5A) have been reported to contribute to high glucose-mediated endothelial injury and epithelial-to-mesenchymal transition. In this study, we hypothesize ets1 associates with KMT5A to modulate PFN2 transcription, thus participating in high glucose-mediated EndMT in glomerular endothelial cells. Methods Immunohistochemistry (IHC) was performed to detect protein levels in the kidney tissues and/or aorta tissues of human subjects and rats. Western blot, qPCR and immunofluorescence were performed using human umbilical vein endothelial cells (HUVECs). Chromatin immunoprecipitation (ChIP) assays and dual luciferase assays were performed to assess transcriptional activity. The difference between the groups was compared by two-tailed unpaired t-tests or one-way ANOVAs. Results Our data indicated that vimentin, αSMA, S100A4 and PFN2 levels were increased, and CD31 levels were reduced in glomerular endothelial cells of DN patients and rats. Our cell experiments showed that high glucose induced EndMT by augmenting PFN2 expression in HUVECs. Moreover, high glucose increased ets1 expression. si-ets1 suppressed high glucose-induced PFN2 levels and EndMT. ets1 overexpression-mediated EndMT was reversed by si-PFN2. Furthermore, ets1 was determined to associate with KMT5A. High glucose attenuated KMT5A levels and histone H4 lysine 20 methylation (H4K20me1), one of the downstream targets of KMT5A. KMT5A upregulation suppressed high glucose-induced PFN2 levels and EndMT. sh-KMT5A-mediated EndMT was counteracted by si-PFN2. Furthermore, H4K20me1 and ets1 occupied the PFN2 promoter region. sh-KMT5A cooperated with ets1 overexpression to activate PFN2 promoter activity. Our in vivo study demonstrated that KMT5A was reduced, while ets1 was augmented, in glomerular endothelial cells of DN patients and rats. Conclusions The present study indicated that ets1 cooperated with KMT5A to transcribe PFN2, thus contributing to hyperglycemia-induced EndMT in the glomerular endothelial cells of DN patients and rats. Trial registration ChiCTR, ChiCTR2000029425. 2020/1/31, http://www.chictr.org.cn/showproj.aspx?proj=48548

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Section: Occurrence Of Endmt and Increase In Pfn2 Expression In Dn Patients And Ratsmentioning

confidence: 88%

“…2A-E). Previous research indicated that PFN2 participates in epithelialto-mesenchymal transition (Tang et al 2015;Zhang et al 2018). Therefore, PFN2 expression was detected in HUVECs.…”

Section: High-glucose Treatment Induced Endmt Via An Increase In Pfn2 Levels In Huvecsmentioning

confidence: 92%

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ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy

Zhong

et al. 2021

Mol Med

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“…On the other hand, the loss of profilin 2 contributes to enhanced EMT and metastasis of colorectal cancer. Thus, the prognostic value of Pfn2 is still controversial [ 208 , 209 ].…”

Section: Actin-related Regulatory Functions That Control Tgfβ Signmentioning

confidence: 99%

Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links

Melchionna¹,

Trono

Tocci³

et al. 2021

Biomolecules

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Human tissues, to maintain their architecture and function, respond to injuries by activating intricate biochemical and physical mechanisms that regulates intercellular communication crucial in maintaining tissue homeostasis. Coordination of the communication occurs through the activity of different actin cytoskeletal regulators, physically connected to extracellular matrix through integrins, generating a platform of biochemical and biomechanical signaling that is deregulated in cancer. Among the major pathways, a controller of cellular functions is the cytokine transforming growth factor β (TGFβ), which remains a complex and central signaling network still to be interpreted and explained in cancer progression. Here, we discuss the link between actin dynamics and TGFβ signaling with the aim of exploring their aberrant interaction in cancer.

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“…PFN2 was also shown to positively correlate with invasion depth and lymph node metastasis and acts as an independent prognostic factor for poor overall survival in ESCC 16 . However, one study found that the expression of PFN2 was downregulated in metastatic colon cancer, and low PFN2 expression was correlated with enhanced EMT in CRC cells 19 . While PFN2 expression may be cancer type and stage specific, how its level changes in tumors remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Profilin 2 Promotes Proliferation and Metastasis of Head and Neck Cancer Cells by Regulating PI3K/AKT/β-Catenin Signaling Pathway

Zhou

Chen

et al. 2019

oncol res

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Profilin 2 (PFN2) was found to be mainly expressed in neurons and involved in the development of the brain. In recent years, emerging evidence indicated that PFN2 is also significantly upregulated in various cancers including head and neck cancer (HNSC) and influences cancer cell proliferation, migration, and invasion. However, the role of PFN2 in HNSC development and progression remains unclear. The aim of our study was to investigate the role of PFN2 in the development of HNSC and its possible molecular mechanisms. Bioinformatics showed that increased expression of PFN2 in tumors correlated highly with poor prognosis of HNSC patients. Our results indicated that PFN2 was highly expressed in HNSC tissues and in HNSC cell lines. Knockdown of PFN2 inhibited proliferation, invasion, and migration of HNSC cells, while PFN2 overexpression produced the opposite effects. Using a nude mouse xenograft model, we substantiated the tumor-promoting effect of PFN2 on HNSC in vivo. Furthermore, we found that PFN2 downregulation reduced the phosphorylation of Akt and GSK-3β and reduced the expression of β-catenin in HNSC cells. The opposite was observed when PFN2 was overexpressed. Collectively, these results suggest that PFN2 promotes the proliferation and metastasis of HNSC by activating the PI3K/Akt/β-catenin signaling pathway. Although further validation is needed, we speculate that PFN2 plays a crucial role in HNSC and may be a promising therapeutic target and prognostic biomarker.

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Loss of profilin�2 contributes to enhanced epithelial-mesenchymal transition and metastasis of colorectal cancer

Cited by 18 publications

References 37 publications

ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy

ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy

Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links

Profilin 2 Promotes Proliferation and Metastasis of Head and Neck Cancer Cells by Regulating PI3K/AKT/β-Catenin Signaling Pathway

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