Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer

Shimada, Hiroshi; Abe, Shyuetsu; Kohno, Takayuki; Satohisa, Seiro; Konno, Takumi; Takahashi, Syunta; Hatakeyama, Tsubasa; Arimoto, Chihiro; Kakuki, Takuya; Kaneko, Yakuto; Takano, Kenichi; Saito, Tsuyoshi; Kojima, Takashi

doi:10.1038/srep37049

Cited by 39 publications

(55 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An inverse correlation has been observed between epithelial cell motility and cell density . RNA interference–mediated knockdown of LSR enhanced cell motility and invasiveness in the Sawano endometrial cancer cell line . To examine whether the LSR localization was sensitive to cell density, we observed the localization of endogenous LSR or tricellulin at different densities of Sawano cells using confocal microscopy.…”

Section: Resultsmentioning

confidence: 99%

“…28,29 RNA interference-mediated knockdown of LSR enhanced cell motility and invasiveness in the Sawano endometrial cancer cell line. 4 To examine whether the LSR localization was sensitive to cell density, we observed the localization of endogenous LSR or tricellulin at different densities of Sawano cells using confocal microscopy. As shown in Figure 1A, both LSR (left panels) and tricellulin (right panels) localized to tricellular contacts at high cell densities (upper panels).…”

Section: Resultsmentioning

confidence: 99%

“…LSRs have been shown to interact directly with tricellulin when they are expressed exogenously in HEK293 cells . It was reported recently that, in Sawano cancer cells, endogenous LSRs form complexes with tricellulin, angiomotin, merlin, and phosphorylated Yes‐associated protein . In LSR‐knockdown cells, tricellulin does not accumulate in tricellular contact regions, indicating that LSR recruits tricellulin to the tricellular contacts .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The bicellular tensile force sorts the localization of LSRs in bicellular and tricellular junctions

Kohno

Kikuchi

Ninomiya

et al. 2017

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

Lipolysis-stimulated lipoprotein receptors (LSRs) localize to tricellular tight junctions. Recent studies have shown that changes in the localization and expression profiles of LSRs are associated with malignancy of endometrial carcinomas, although the precise mechanisms by which malignant progression induces changes in the localization of LSRs are still unknown. In this study, we found that changes in cell tension correlated with alterations in the junctional localization of LSRs in endometrial cancer Sawano cells. At high cell densities, myosin phosphatase target subunit 1 (MYPT1) localized to bicellular junctions, whereas activated myosin regulatory light chain 2 (MRLC2) was dislocated from these regions, suggesting that circumferential tensile forces decreased at high cell densities. Under these conditions, LSRs localized to tricellular junctions. In contrast, a phosphorylated form of MRLC2 localized to bicellular regions, while MYPT1 was excluded from these regions, suggesting that tensile forces formed along the circumferential edge at low cell densities. It is noteworthy that, when cells were cultured under these conditions, LSRs localized to bicellular regions. Upon treatment with a myosin inhibitor, LSR localization in bicellular junctions decreased at low cell densities. Overall, our results indicate that the modulation of cellular tension was involved in the translocation of LSRs from bicellular to tricellular tight junctions.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The bicellular tensile force sorts the localization of LSRs in bicellular and tricellular junctions

Kohno

Kikuchi

Ninomiya

et al. 2017

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

show abstract

“…Wound healing assays were carried out as described previously . Cells were seeded in 6‐well plates (1 × 10 5 cells/well) and cultured at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…Wound healing assays were carried out as described previously. 39,40 Cells were seeded in 6-well plates (1 × 10 5 cells/well) and cultured at 37°C. After 24 hours, a pipette tip was used to create a wound in the cell monolayer.…”

Section: Wound Healing Assaymentioning

confidence: 99%

G9a and histone deacetylases are crucial for Snail2‐mediated E‐cadherin repression and metastasis in hepatocellular carcinoma

Zheng

Dai

et al. 2019

Cancer Science

View full text Add to dashboard Cite

Functional E‐cadherin loss, a hallmark of epithelial‐mesenchymal transition (EMT), is important for metastasis. However, the mechanism of Snail2 in hepatocellular carcinoma (HCC) EMT and metastasis remains unclear. Here, we showed that Snail2 was upregulated in primary HCC, and significantly increased during transforming growth factor‐β‐induced liver cell EMT. Snail2‐overexpressing and knockdown cell lines have been established to determine its function in EMT in HCC. H3K9 methylation was upregulated and H3K4 and H3K56 acetylation were downregulated at the E‐cadherin promoter in Snail2‐overexpressing cancer cells. Furthermore, Snail2 interacted with G9a and histone deacetylases (HDACs) to form a complex to suppress E‐cadherin transcription. Snail2 overexpression enhanced migration and invasion in HCC cells, whereas G9a and HDAC inhibition significantly reversed this effect. Moreover, Snail2 overexpression in cancer cells increased tumor metastasis and shortened survival time in mice, whereas G9a and HDAC inhibitors extended survival. Our study not only reveals a critical mechanism underlying the epigenetic regulation of EMT but also suggests novel treatment strategies for HCC.

show abstract

Potentiation of cancerous progression by LISCH7 via direct stimulation of TGFB1 transcription in triple‐negative breast cancer

Tang

Zhou

Liu

et al. 2020

J of Cellular Biochemistry

View full text Add to dashboard Cite

As an aggressive breast cancer (BCa) subtype, triple‐negative breast cancer (TNBC) responses poorly to chemotherapy and endocrine therapy, and usually has a worse prognosis. This is largely due to the lack of specific therapeutic targets, laying claim to an imperious demand to clarify the key signaling pathways potentiating TNBC progression. Herein, we report that expression levels of the liver‐specific bHLH‐Zip transcription factor (LISCH7), a recently identified key player in cancerous progression, preferentially enriched in TNBC in comparison with other BCa subtypes, and this upregulation was observed to be correlated to a poor survival outcome in patients with TNBC. Ablation of LISCH7 in TNBC cells impaired cell proliferation, reduced cell invasiveness, and enhanced sensitivity to the first‐line chemotherapeutic drug docetaxel at both in vitro and in vivo levels. Importantly, concurrent induction of TGFB1, the gene encoding transforming growth factor‐β1 (TGF‐β1), an essential multipluripotent regulator of TNBC, was accompanied with these alterations in cancerous properties. We further showed that LISCH7 could directly bind to the TGFB1 promoter and stimulate TGFB1 transcription in TNBC cells. The recruitment of LISCH7 onto the TGFB1 chromatin and transactivation of TGFB1 were substantially augmented by treatment with the exogenous TGF‐β1 in a time‐ and dose‐dependent manner. Collectively, these findings suggest that LISCH7 and TGF‐β1 form a reciprocal positive regulatory loop and cooperatively regulate cancerous progression in TNBC cells. Thus, simultaneous inhibition of both LISCH7 and TGF‐β1 signaling may represent a more effective approach to counteract advanced TNBC.

show abstract

Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer

Cited by 39 publications

References 33 publications

The bicellular tensile force sorts the localization of LSRs in bicellular and tricellular junctions

The bicellular tensile force sorts the localization of LSRs in bicellular and tricellular junctions

G9a and histone deacetylases are crucial for Snail2‐mediated E‐cadherin repression and metastasis in hepatocellular carcinoma

Potentiation of cancerous progression by LISCH7 via direct stimulation of TGFB1 transcription in triple‐negative breast cancer

Contact Info

Product

Resources

About