SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model

Su, Feng; Geng, Jing; Li, Xinying; Qiao, Chuan; Luo, Longlong; Feng, Jie; Dong, Xin-Jun; Lv, Ming

doi:10.3892/or.2017.5998

Cited by 36 publications

(27 citation statements)

References 24 publications

(33 reference statements)

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“…SP1 affects the growth and metastasis of tumors by regulating the expressions of tumor‐related genes . It can bind to specific sites on the promoter of vascular endothelial growth factor (VEGF) or VEGF receptor, which further promotes the progress of tumors . SP1‐regulated tumor‐related genes are involved in a variety of cell functions, including cell cycle (Cyclin D1, TGF‐α, E2F1), apoptosis (Bax, Bcl2), tumor metastasis (TGF‐β, MMP2) and angiogenesis (VEGF) .…”

Section: Discussionmentioning

confidence: 71%

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Xia

et al. 2019

Cancer Medicine

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Syncytin 1 is considered as an oncogene in various malignant tumors, but its effect on non‐small cell lung cancer (NSCLC) has not been reported. We investigated the specific role of Syncytin 1 on NSCLC through the transfection of Syncytin 1 knockdown or overexpression plamids in A549 cells. Our results proved that knockdown of Syncytin 1 inhibited the proliferation, and blocked the cell cycle on G1 phase by inhibiting the expression of Nusap1, Cyclin D1, CDK6, and CDK4. Cell cycle arrest also leaded to increased apoptosis in Syncytin 1 knockdown cells. Suppression of Syncytin 1 inhibited the migration and invasion, as well as the expressions of epithelial‐mesenchymal transition (EMT) makers, N‐cadherin, β‐catenin, and Vimentin, indicating that Syncytin 1 knockdown inhibited the metastasis via reversing the EMT process in A549 cells. The phosphorylation levels of Akt, mTOR, and Erk1/2 were all decreased in Syncytin 1 knockdown cells, suggesting the signaling pathways by which Syncytin 1 operated as an oncogene in NSCLC. Moreover, the underexpression of transcription factor SP1 downregulated the Syncytin 1 expression in A549 cells. The rescue experiment of Syncytin 1 in SP1 knockdown cells further proved that Syncytin 1 could block the inhibition of cell growth induced by SP1 knockdown. In conclusion, knockdown of SP1/Syncytin1 axis inhibited the progression of NSCLC by the reversion of tumor epithelial‐mesenchymal transition process and suppression of Akt and Erk signaling pathways, suggesting that they are potential targets for targeted therapy of NSCLC.

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Section: Discussionmentioning

confidence: 71%

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Xia

et al. 2019

Cancer Medicine

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“…The cross‐talk between the cancer cells and their environment involves numerous oncogenic transcription factors. These factors are aberrantly reactivated and trigger a series of cellular events such as genome instability, reprogrammed metabolism, infinite proliferation, angiogenesis, invasion and metastasis, immune cell infiltration, and enhanced inflammation, all of which have been widely recognized as the characteristics of cancer …”

Section: Introductionmentioning

confidence: 99%

Role of telomerase in the tumour microenvironment

Liu

Guo

Liu

et al. 2019

Clin Exp Pharma Physio

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The tumour mass is an organ-like structure consisting of cancer cells and their directly associated microenvironment. The tumour microenvironment (TME) is the local environment where malignant cells strive and survive, and is composed of cancers cells and their surroundings such as blood vessels, extracellular matrix (ECM), infiltrating immune cells, fibroblasts, and signalling molecules. 1,2 In addition, cancer stem cells (CSCs) and endoplasmic reticulum (ER) stress influence the properties of the TME to benefit tumour cell growth. 3,4 The cross-talk between the cancer cells and their environment involves numerous oncogenic transcription factors. These factors are aberrantly reactivated and trigger a series of cellular events such as genome instability, reprogrammed metabolism, infinite proliferation, angiogenesis, invasion and metastasis, immune cell infiltration, and enhanced inflammation, all of which have been widely recognized as the characteristics of cancer. Telomeres consist of a non-coding DNA tandem repeat of sequence 5′-TTAGGG-3′, located at the ends of the linear eukaryotic chromosomes. 26,27 Due to "the end replication problem", the telomeres shorten with each round of DNA replication. Once their lengths shorten to a certain level, the cells may undergo replicative senescence. 26,28 Telomerase is an RNA-dependent DNA polymerase that synthesizes telomeric DNA sequences and maintains the telomere length, providing the immortal cells with the molecular basis for unlimited proliferation potential. Human telomerase essentially AbstractTelomeres are specialized genomic structures that protect chromosomal ends to maintain genomic stability. Telomeric length is primarily regulated by the telomerase complex, essentially consisting of an RNA template (TERC), an enzymatic subunit (telomerase reverse transcriptase, TERT). In humans, telomerase activity is repressed during embryonic differentiation and is absent in most somatic cells. However, it is upregulated or reactivated in 80%-90% of the primary tumours in humans. The human TERT (hTERT) plays a pivotal role in cellular immortality and tumourigenesis.However, the molecular mechanisms of telomerase functioning in cancer have not been fully understood beyond the telomere maintenance. Several research groups, including ours, have demonstrated that hTERT possesses vital functions independent of its telomere maintenance, including angiogenesis, inflammation, cancer cell stemness, and epithelial-mesenchymal transformation (EMT). All these telomereindependent activities of hTERT may contribute to the regulation of the dynamics and homeostasis of the tumour microenvironment (TME), thereby promoting tumour growth and development. Cancer progression and metastasis largely depend upon the interactions between cancer cells and their microenvironment. In this review, the involvement of TERT in the tumour microenvironment and the underlying implications in cancer therapeutics have been summarized. K E Y W O R D Sangiogenesis, inflammation, telomerase, TERT, tumour micro...

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“…For example, SP1 was overexpression in breast cancer and could regulate TINCR- MIR - 7 -KLF4 axis, which in turn stimulate cell proliferation but suppress cell apoptosis [ 7 ]. In ovarian cancer, upregulation of SP1 enhanced VEGF expression and resulted in angiogenesis and migration stimulation in vitro and in vivo [ 8 ]. Another study investigated the role of SP1 in hepatocellular carcinoma demonstrated that SP1 regulate cystathionine γ-lyase gene expression in human hepatocellular carcinoma cell lines to promote cell proliferation and cell cycle progression [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-382 inhibits cell growth and migration in colorectal cancer by targeting SP1

2018

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BackgroundEmerging evidence showed that microRNAs (miRs) play critical roles in human cancers by functioning as either tumor suppressor or oncogene. MIR-382 was found to function as tumor suppressor in certain cancers. However, the role of MIR-382 in colorectal cancer (CRC) is largely unknown. Specificity protein 1 (SP1) is highly expressed in several cancers including CRC and is correlated with poor prognosis, but it is unclear whether or not MIR-382 can regulate the expression of SP1.MethodsMIR-382 expression level was measured by reverse transcription-quantitative polymerase chain reaction. The connection between MIR-382 and SP1 was validated by luciferase activity reporter assay and western blot assay. Cell counting kit-8 assay and wound-healing assay were conducted to investigate the biological functions of MIR-382 in CRC.ResultsIn this study, we found MIR-382 expression was downregulated in CRC tissues and cell lines, and the transfection of MIR-382 mimic decreased cell growth and migration. Furthermore, we identified SP1 was a direct target of MIR-382. Overexpression of MIR-382 decreased the expression of SP1, whereas MIR-382 knockdown promoted SP1 expression. We also observed an inversely correlation between MIR-382 and SP1 in CRC tissues. Additionally, we showed that knockdown of SP1 inhibited cell growth and migration and attenuated the effect of MIR-382 inhibitor on cell behaviors.ConclusionsIn conclusion, the present study describes a potential mechanism underlying a MIR-382/SP1 link contributing to CRC development. Thus, MIR-382 may be able to be developed as a novel treatment target for CRC.

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SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model

Cited by 36 publications

References 24 publications

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Role of telomerase in the tumour microenvironment

MicroRNA-382 inhibits cell growth and migration in colorectal cancer by targeting SP1

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