Fascin‐1 as a novel diagnostic marker of triple‐negative breast cancer

Wang, Chao Qun; Tang, Chih Hsin; Chang, Hao Teng; Li, Xiao Ni; Zhao, Yong; Su, Chen; Hu, Guoqing; Zhang, Tao; Sun, Xuejing; Zeng, Yue; Du, Zhanhui; Wang, Yan; Huang, Bifei

doi:10.1002/cam4.746

Cited by 49 publications

(49 citation statements)

References 17 publications

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“…The high frequency of KRAS or BRAF mutations confers SAC with an important resistance to current anti-epidermal growth factor receptor therapies 9,10 . Similarly, several authors have reported that fascin1 is overexpressed in triple negative/basal phenotype breast carcinoma [22][23][24] . Given the role of fascin1 in invasion and metastasis, we performed a bioinformatic search for in silico identification of chemical compounds blocking this protein.…”

Section: Discussionmentioning

confidence: 70%

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

Alburquerque-González

Bernabé-García

Montoro-García

et al. 2020

Exp Mol Med

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Serrated adenocarcinoma (SAC) is more invasive, has worse outcomes than conventional colorectal carcinoma (CRC), and is characterized by frequent resistance to anti-epidermal growth factor receptor (EGFR) and overexpression of fascin1, a key protein in actin bundling that plays a causative role in tumor invasion and is overexpressed in different cancer types with poor prognosis. In silico screening of 9591 compounds, including 2037 approved by the Food and Drug Administration (FDA), was performed, and selected compounds were analyzed for their fascin1 binding affinity by differential scanning fluorescence. The results were compared with migrastatin as a typical fascin1 inhibitor. In silico screening and differential scanning fluorescence yielded the FDA-approved antidepressant imipramine as the most evident potential fascin1 blocker. Biophysical and different in vitro actin-bundling assays confirm this activity. Subsequent assays investigating lamellipodia formation and migration and invasion of colorectal cancer cells in vitro using 3D human tissue demonstrated anti-fascin1 and anti-invasive activities of imipramine. Furthermore, expression profiling suggests the activity of imipramine on the actin cytoskeleton. Moreover, in vivo studies using a zebrafish invasion model showed that imipramine is tolerated, its anti-invasive and antimetastatic activities are dose-dependent, and it is associated with both constitutive and induced fascin1 expression. This is the first study that demonstrates an antitumoral role of imipramine as a fascin1 inhibitor and constitutes a foundation for a molecular targeted therapy for SAC and other fascin1-overexpressing tumors.

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Section: Discussionmentioning

confidence: 70%

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

Alburquerque-González

Bernabé-García

Montoro-García

et al. 2020

Exp Mol Med

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“…We also enrolled 154 untreated women scheduled for breast cancer surgery at the Affiliated Dongyang Hospital of Wenzhou Medical University (Dongyang, Zhejiang, China) between 2007 and 2017; one tissue specimen was obtained from each participant. Tumor grades were assigned using the Scarff-Bloom-Richardson system and the World Health Organization breast tumor classification criteria were used for pathohistological diagnosis [23] Cases were assigned estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 status and subtyped as Luminal A (ER-positive [+] and/or PR + , HER2-negative [-], Ki-67 <14%), Luminal B (ER + and/or PR + , HER2 -, Ki-67 ≥14%, ER + and/or PR + , HER2 + ), HER2-enriched (ER -, PR -, HER2 + ), or as triple-negative breast cancer (TNBC; ER -, PR -, HER2 -) [24,25,26]. Clinicopathological information was collected from electronic medical records and at study entry each study participant completed a standardized questionnaire providing sociodemographic data.…”

Section: Participantsmentioning

confidence: 99%

Impacts of RETN genetic polymorphism on breast cancer development

et al. 2020

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The adipokine resistin is linked with obesity, inflammation and various cancers, including breast cancer. This study sought to determine whether certain polymorphisms in the gene encoding resistin, RETN, increase the risk of breast cancer susceptibility. We analyzed levels of resistin expression in breast cancer tissue and samples from The Cancer Genome Atlas database. We also examined associations between four RETN single nucleotide polymorphisms (SNPs; rs3745367, rs7408174, rs1862513 and rs3219175) and breast cancer susceptibility in 515 patients with breast cancer and 541 healthy women without cancer. Compared with wild-type (GG) carriers, those carrying the AG genotype of the RETN SNP rs3219175 and those carrying at least one A allele in the SNP rs3219175 had a higher chance of developing breast cancer (adjusted odds ratio, AOR: 1.295, 95% confidence intervals, CI: 1.065-1.575 and 2.202, 1.701-2.243, respectively). When clinical aspects and the RETN SNP rs7408174 were examined in the breast cancer cohort, the CT genotype was linked to late-stage disease, while women with luminal A disease and at least one C allele were likely to progress to stage III/IV disease and to develop highly pathological grade III disease. Moreover, resistin-positive individuals were at greater risk than resistin-negative individuals for developing pathological grade III disease (OR: 5.020; 95% CI: 1.380-18.259). This study details risk associations between resistin and RETN SNPs in breast cancer susceptibility in Chinese Han women.

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“…Previous studies have showed that both the expression of fascin-1 and laminin-5 were associated with the invasiveness and prognoses of several cancers, including colorectal (Adams, 2015;Fukazawa et al, 2015), gastric (Saito et al, 2010;Tu et al, 2016), pancreatic (Tsai et al, 2013;Chen et al, 2015) cancers and breast adenocarcinomas (D'Alfonso et al, 2015;Wang et al, 2016). Recently, some authors reported that the expression of fascin-1 and laminin-5 were associated with clinico-pathological characteristics of non-small cell lung cancer (Moriya et al, 2001;Niki et al, 2002;Pelosi et al, 2003;Choi et al, 2006;An et al, 2012;Ling et al, 2015;Luo et al, 2015;Zhao et al, 2015;Liu et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of fascin-1 and laminin-5 in non-small cell lung cancer

Yang¹,

Teng²,

Han³

et al. 2017

Genet. Mol. Res.

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Lung cancer is the leading cause of cancer death in men and the second leading cause of cancer death in women worldwide. Fascin-1 and laminin-5 were associated with the invasiveness and prognoses of several cancers. The expression and the serum levels of fascin-1 and laminin-5 in patients with non-small cell lung cancer (NSCLC) were analyzed in this study. The expression of fascin-1 and laminin-5 were examined in 378 patients and their serum level was measured in 154 patients. The health of all patients was followed post-surgery. The expression of fascin-1 (P = 0.000) and lanminin-5 (P = 0.001) and the serum levels of fascin-1 (P = 0.015) and laminin-5 (P = 0.046) were related to the relapse of patients with NSCLC. Both serum levels and expression of fascin-1 and laminin-5 can be used to effectively evaluate the prognoses of patients with NSCLC.

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Fascin‐1 as a novel diagnostic marker of triple‐negative breast cancer

Cited by 49 publications

References 17 publications

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

Impacts of RETN genetic polymorphism on breast cancer development

Clinical significance of fascin-1 and laminin-5 in non-small cell lung cancer

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