Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes

Scott, Kenneth L.; Nogueira, Cristina; Heffernan, Timothy P.; Doorn, Remco van; Dhakal, Sabin; Hanna, Jason A.; Min, Chengyin; Jaskelioff, Mariela; Xiao, Yonghong; Wu, Chang Jiun; Cameron, Lisa; Perry, Samuel R.; Zeid, Rhamy; Feinberg, Tamar; Kim, Minjung; Woude, George Vande; Granter, Scott R.; Bosenberg, Marcus W.; Chu, Gerald C.; DePinho, Ronald A.; Rimm, David L.; Chin, Lynda

doi:10.1016/j.ccr.2011.05.025

Cited by 129 publications

(155 citation statements)

References 47 publications

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“…The human FSCN1 expression vector pLenti6/V5-DEST-FASCIN was a gift from Lynda Chin (Addgene, #31207) [19]. SKOV3 and 3AO cells were seeded into 6-well plates until 70 %-90 % confluency and transiently transfected with pLenti6/V5-DEST-FASCIN or control vector 3μg per well using the X-treme GENE HP DNA Transfection Reagent (Roche, Indianapolis, IN, USA) following the manufacturer's protocol.…”

Section: Plasmid Transfectionmentioning

confidence: 99%

FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in Ovarian Cancer Cells

Zhang

Pei

et al. 2018

Cell Physiol Biochem

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Background/Aims: Epithelial-mesenchymal transition (EMT) is one of the key mechanisms mediating cancer progression. Snail1 has a pivotal role in the regulation of EMT, involving the loss of E-cadherin and concomitant upregulation of vimentin, among other biomarkers. We have found FSCN1 promoted EMT in ovarian cancer cells, but the precise mechanism of FSCN1 in EMT process has not been clearly elucidated. Methods: The levels of FSCN1 and snail1 were determined in epithelial ovarian cancer(EOC) specimen and in ovarian cancer cells by RT-qPCR. The changes of EMT makers and effects on snail1 by FSCN1 were examined by overexpression or depletion of FSCN1 in EOC cells by RT-qPCR and western blotting. The invasiveness of the FSCN1-modified EOC cells was examined in transwell assay. Co-immunoprecipitation (IP) was performed to detect the interaction between snail1 and FSCN1 in EOC cells. Results: We found FSCN1 and snail1 significantly increased in EOC, and especially in EOC with metastasis. FSCN1 was positively correlated with snail1 expression at the cellular/histological levels. Moreover, we further showed that FSCN1 physiologically interacted with and increased the levels of snail1 to promote ovarian cancer cell EMT. Conclusion: FSCN1 promote EMT through snail1 in ovarian cancer cells. FSCN1 is an attractive novel target for inhibiting invasion and metastasis of EOC cells.

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Section: Plasmid Transfectionmentioning

confidence: 99%

FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in Ovarian Cancer Cells

Zhang

Pei

et al. 2018

Cell Physiol Biochem

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“…A high migration potential is thought to be a prerequisite for tumor cell invasion and spread, hence suggesting the involvement of HSF1 in the regulation of cancer metastasis. Importantly, HSF1 was found among six metastasis-promoting genes in malignant melanomas [34]. Its ability to promote migration and invasion was also observed in hepatocellular carcinomas [8].…”

Section: Introductionmentioning

confidence: 95%

Active heat shock transcription factor 1 supports migration of the melanoma cells via vinculin down-regulation

Toma-Jonik

Widłak

Korfanty

et al. 2015

Cellular Signalling

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Heat shock transcription factor 1 (HSF1), the major regulator of stress response, is frequently activated in cancer and has an apparent role in malignant transformation. Here we analyzed the influence of the over-expression of a constitutively active transcriptionally-competent HSF1 mutant form on phenotypes of mouse and human melanoma cells. We observed that the expression of active HSF1 supported anchorage-independent growth in vitro, and metastatic spread in the animal model in vivo, although the proliferation rate of cancer cells was not affected. Furthermore, active HSF1 enhanced cell motility, reduced the adherence of cells to a fibronectin-coated surface, and affected the actin cytoskeleton. We found that although the expression of active HSF1 did not affect levels of epithelial-to-mesenchymal transition markers, it caused transcriptional down-regulation of vinculin, protein involved in cell motility, and adherence. Functional HSF1-binding sites were found in mouse and human Vcl/VCL genes, indicating a direct role of HSF1 in the regulation of this gene. An apparent association between HSF1-induced down-regulation of vinculin, increased motility, and a reduced adherence of cells suggests a possible mechanism of HSF1-mediated enhancement of the metastatic potential of cancer cells.

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“…Recently it has been shown to play a fundamental role in tumor biology (Dai et al, 2007; Jin et al, 2011). In a wide variety of human cancer cell lines, the depletion of HSF1 markedly reduces growth, survival and metastatic potential (Mendillo et al, 2012; Meng et al, 2010; Santagata et al, 2012; Scott et al, 2011). Hsf1 null mice develop normally, but are profoundly resistant to tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, it acts to support the malignant state by blunting apoptotic responses and promoting pathways that facilitate anabolic metabolism, protein folding, proliferation, invasion, and metastasis (Dai et al, 2012; Fang et al, 2012; Jin et al, 2011; Mendillo et al, 2012; Meng et al, 2010; Santagata et al, 2013; Scott et al, 2011). In humans, activation of this program by HSF1 in cancer cells is strongly associated with disease progression in patients with breast, colon, lung, and hepatocellular carcinomas (Fang et al, 2012; Mendillo et al, 2012; Santagata et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The Reprogramming of Tumor Stroma by HSF1 Is a Potent Enabler of Malignancy

Scherz-Shouval

Santagata

Mendillo

et al. 2014

Cell

321

282

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Summary Stromal cells within the tumor microenvironment are essential for tumor progression and metastasis. Surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors. We report that the transcriptional regulator Heat-Shock Factor 1 (HSF1) is frequently activated in cancer-associated fibroblasts (CAFs), where it is a potent enabler of malignancy. HSF1 drives a transcriptional program in CAFs that complements, yet is completely different from, the program it drives in adjacent cancer cells. This CAF program is uniquely structured to support the malignant potential of cancer cells in a non-cell-autonomous way. Two central stromal signaling molecules—TGFβ and stromal-derived factor 1 (SDF1) – play a critical role. In early stage breast and lung cancer, high stromal HSF1 activation is strongly associated with poor patient outcome. Thus, tumors co-opt the ancient survival functions of HSF1 to orchestrate malignancy in both cell-autonomous and non-cell-autonomous ways, with far-reaching therapeutic implications.

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Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes

Cited by 129 publications

References 47 publications

FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in Ovarian Cancer Cells

FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in Ovarian Cancer Cells

Active heat shock transcription factor 1 supports migration of the melanoma cells via vinculin down-regulation

The Reprogramming of Tumor Stroma by HSF1 Is a Potent Enabler of Malignancy

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