<scp>TGF</scp>‐β transactivates <scp>EGFR</scp> and facilitates breast cancer migration and invasion through canonical Smad3 and <scp>ERK</scp>/Sp1 signaling pathways

Zhao, Yuanyuan; Ma, Jing; Fan, Yonggang; Wang, Zhiyong; Tian, Ran; Ji, Wei; Zhang, Fei; Niu, Ruifang

doi:10.1002/1878-0261.12162

Cited by 138 publications

(98 citation statements)

References 44 publications

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“…Western blot assay was performed as described previously [44]. Briefly, the cells were lysed with 1× SDS lysis buffer; the cell lysates after protein quantification were used for SDS-PAGE separation and subsequently transferred to a PVDF membrane.…”

Section: Western Blot and Co-immunoprecipitation Assaymentioning

confidence: 99%

Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells

Fan

et al. 2019

Breast Cancer Res

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Background: Acquirement of resistance is always associated with a highly aggressive phenotype of tumor cells. Recent studies have revealed that Annexin A2 (Anxa2) is a key protein that links drug resistance and cancer metastasis. A high level of Anxa2 in cancer tissues is correlated to a highly aggressive phenotype. Increased Anxa2 expression appears to be specific in many drug-resistant cancer cells. The functional activity of Anxa2 is regulated by tyrosine phosphorylation at the Tyr23 site. Nevertheless, the accurate molecular mechanisms underlying the regulation of Anxa2 tyrosine phosphorylation and whether phosphorylation is necessary for the enhanced invasive phenotype of drug-resistant cells remain unknown. Methods: Small interfering RNAs, small molecule inhibitors, overexpression, loss of function or gain of function, rescue experiments, Western blot, wound healing assays, transwell assays, and in vivo metastasis mice models were used to investigate the functional effects of Rack1 and Src on the tyrosine phosphorylation of Anxa2 and the invasion and metastatic potential of drug-resistant breast cancer cells. The interaction among Rack1, Src, and Anxa2 in drug-resistant cells was verified by co-immunoprecipitation assay. Results: We demonstrated that Anxa2 Tyr23 phosphorylation is necessary for multidrug-resistant breast cancer invasion and metastasis. Rack1 is required for the invasive and metastatic potential of drug-resistant breast cancer cells through modulating Anxa2 phosphorylation. We provided evidence that Rack1 acts as a signal hub and mediates the interaction between Src and Anxa2, thereby facilitating Anxa2 phosphorylation by Src kinase. Conclusions: Our findings suggest a convergence point role of Rack1/Src/Anxa2 complex in the crosstalk between drug resistance and cancer aggressiveness. The interaction between Anxa2 and Rack1/Src is responsible for the association between drug resistance and invasive/metastatic potential in breast cancer cells. Thus, our findings provide novel insights on the mechanism underlying the functional linkage between drug resistance and cancer aggressiveness.

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Section: Western Blot and Co-immunoprecipitation Assaymentioning

confidence: 99%

Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells

Fan

et al. 2019

Breast Cancer Res

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“…Abnormal expression of SP1 is often associated with the occurrence and progression of tumors. Many studies have shown that the expression of SP1 in gastric cancer [12], pancreatic cancer [13] and breast cancer [14] is significantly higher than that in corresponding normal tissues. Inhibition of SP1 expression could significantly impede cell proliferation and cell cycle progression in TSCC cell lines [15].…”

Section: Introductionmentioning

confidence: 99%

Association of SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms with human tongue squamous cell carcinoma

Lai

Meng³

et al. 2019

Bioscience Reports

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Objective: To study the association between SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms and risk of human tongue squamous cell carcinoma (TSCC). Methods: Sanger sequencing was used to determine the genotypes of SP1 rs1353058818 and STAT3 rs1053004 loci in 240 TSCC patients and 240 controls. Levels of hsa-miR-149-5p and hsa-miR-21-5p and expression levels of SP1 and STAT3 proteins in tumor tissues and adjacent normal tissues of TSCC patients were ascertained. Results: Carrying the SP1 rs1353058818 locus deletion allele was a high risk factor for TSCC (OR = 2.997, 95% CI: 1.389–6.466, P = 0.003). The STAT3 rs1053004 locus A allele was a protective factor for TSCC (OR = 0.604, 95% CI: 0.460-0.793, P < 0.001). There was a negative correlation between SP1 mRNA and hsa-miR-149-5p in tumor and adjacent normal tissues (r = −0.81, −0.77). The expression of SP1 protein in tumor tissues of the SP1 rs1353058818 locus DD genotype was significantly higher than in tissues of the ID type, and in tissues of type II it was the lowest. STAT3 mRNA was positively correlated with hsa-miR-21-5p in tumor and adjacent normal tissues (r = 0.75, 0.78). The expression level of STAT3 protein in tumor tissues of patients with STAT3 rs1053004 locus GG genotype was significantly higher than in patients with type GA, and it was the lowest in patients with type AA. Conclusion: Polymorphisms in the SP1 rs1353058818 and STAT3 rs1053004 loci are associated with the risk of human TSCC.

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“…SMAD3 is a member of the SMAD3 family which functions as a direct mediator of TGFnucleus [27]. Alteration of the TGF-, and invasion of different types of cancers, like breast cancer and glioma [28,29]. Zhao et al found that SMAD3 could be regulated by TCF and JUN through interactions with histone deacet ylases and acetyltransferases [30].…”

Section: Discussionmentioning

confidence: 99%

LncRNA CDKN2B-AS1 promotes the progression of ovarian cancer by miR-143-3p/SMAD3 axis and predicts a poor prognosis

Xu¹,

Zhai²,

Fu³

2020

neo

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Long noncoding RNAs (LncRNAs) show great potential as the therapeutic targets attributing to their implication in the progression of various human cancers, including ovarian cancer (OC). Here, we aimed to explore the biological function of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in OC and its mechanism of action. The abundances of CDKN2B-AS1, miR-143-3p, and SMAD3 mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8) was performed to analyze cell proliferation. Cell apoptosis was assessed by flow cytometry and western blot analyses. Transwell assay was utilized to analyze cell migration and invasion abilities. Tumor xenograft was performed to confirm the role of CDKN2B-AS1 in ovarian tumor growth in vivo. The protein level of SMAD3 was examined by western blot assay. The interaction between CDKN2B-AS1 and miR-143-3p, or miR-143-3p and SMAD3 was demonstrated by bioinformatic, luc iferase reporter, qRT-PCR and western blot analyses. CDKN2B-AS1 was upregulated in OC and correlated with clinicopathologic features. The knockdown of CDKN2B-AS1 hampered the development of OC, as reflected by the suppression of cell proliferation, migration, and invasion, and the enhancement of cell apoptosis, whereas the effects could be rescued by the overexpression of SMAD3. The absence of CDKN2B-AS1 blocked tumor growth in vivo. CDKN2B-AS1 served as a molecular sponge for miR-143-3p, leading to the derepression of miR-143-3p target SMAD3, which eventually triggered the progression of OC. In conclusion, CDKN2B-AS1 promoted tumor growth, invasion, and migration of OC by regulation of miR-143-3p/SMAD3 axis, hinting that CDKN2B-AS1 might be a potential biomarker for OC diagnosis and treatment.

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TGF‐β transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways

Cited by 138 publications

References 44 publications

Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells

Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells

Association of SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms with human tongue squamous cell carcinoma

LncRNA CDKN2B-AS1 promotes the progression of ovarian cancer by miR-143-3p/SMAD3 axis and predicts a poor prognosis

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