Serum starvation regulates E-cadherin upregulation via activation of c-Src in non-small-cell lung cancer A549 cells

Dong, Shuying; Khoo, Andrew; Wei, Jianxin; Bowser, Rachel K.; Weathington, Nathaniel M.; Xiao, Shuqi; Zhang, Lina; Ma, Hu; Zhao, Yutong; Zhao, Jing

doi:10.1152/ajpcell.00132.2014

Cited by 21 publications

(23 citation statements)

References 55 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Down-regulation of E-cadherin expression has been well studied, but few reports have focused on up-regulation of E-cadherin. We have shown that Src kinase up-regulates E-cadherin translation in A549 cells (51). Here, we present evidence that USP48 depletion increases E-cadherin mRNA levels in epithelial cells.…”

Section: Discussionsupporting

confidence: 53%

The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E‐cadherin‐mediated adherens junctions

Wang

Zhao

et al. 2017

FASEB j.

Self Cite

View full text Add to dashboard Cite

The tumor necrosis factor receptor-associated factor 2 (TRAF2) is a second messenger adaptor protein that plays an essential role in propagating TNF-α-mediated signaling pathways. Modulation of TRAF2 activity by ubiquitination is well studied; however, the deubiquitinating enzyme (DUB), which regulates TRAF2 stability, has not been identified. Here we reveal USP48 as the first identified DUB to deubiquitinate and stabilize TRAF2 in epithelial cells. Down-regulation of USP48 increases K48-linked polyubiquitination of TRAF2 and reduces TRAF2 protein levels. Interestingly, USP48 only targets the TRAF2 related to JNK pathway, not the TRAF2 related to NF-κB and p38 pathways. USP48 is serine phosphorylated in response to TNF-α. The phosphorylation is catalyzed by glycogen synthase kinase 3β (GSK3β), ultimately resulting in increases in USP48 DUB activity. Furthermore, we reveal a new biologic function of TRAF2 that contributes to epithelial barrier dysfunction, which is attenuated by knockdown of USP48. Inhibition of TRAF2/JNK pathway increases E (epithelial)-cadherin expression and enhances epithelial barrier integrity, while knockdown of USP48 attenuates TNF-α/JNK pathway and increases E-cadherin expression and cell-cell junction in epithelial cells. These data, taken together, indicate that USP48 stabilizes TRAF2, which is promoted by GSK3β-mediated phosphorylation. Further, down-regulation of USP48 increases E-cadherin expression and epithelial barrier integrity through reducing TRAF2 stability.-Li, S., Wang, D., Zhao, J., Weathington, N. M., Shang, D., Zhao, Y. The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions.

show abstract

Section: Discussionsupporting

confidence: 53%

The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E‐cadherin‐mediated adherens junctions

Wang

Zhao

et al. 2017

FASEB j.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although it is rarely reported that starvation can increase the E-cadherin of PCa cells PC3 and DU145. However, similar reports have been found in other cancer cell studies [33]. Silencing Akt1 suppresses the increased of E-cadherin caused by starvation.…”

Section: Discussionsupporting

confidence: 88%

Silencing Akt1 Inhibits Starvation Induced Lung Metastasis Through Epithelial Mesenchymal Transition Independent of E-cadherin in Prostate Cancer

Yang¹,

Liu²,

Qiu³

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundEpithelial to mesenchymal transition (EMT) of prostate cancer (PCa) cells facilitates their progress to metastasis. We have recently reported Akt1 is an important EMT regulator, and silencing Akt1 induced EMT and inhibited the growth of PCa cells. These results imply Akt1 silencing may increase starvation resistance of PCa cells. However, little is known about the role of Akt1 of PCa cells in starvation.MethodsApoptosis was detected by TUNEL and flow cytometry, cell invasion was detected by transwells and ECIS, lung metastasis was evaluated by tail vein injection animal model, variation of EMT markers was detected by Western-blot.ResultsWe found starvation slowed down the growth and proliferation, and increased apoptosis of PCa cells; Silencing Akt1 gene inhibited these effects of starvation and decreased E-cadherin. Akt1 silencing enhanced invasion induced by starvation of PCa cells in vitro ; however, it inhibited lung metastasis induced by starvation of PCa cells in vivo unexpectedly.ConclusionStarvation or silencing Akt1 alone can promote lung metastasis of PCa cells, however, silencing Akt1 while starving PCa cells can significantly inhibit this function via EMT independent of E-cadherin.

show abstract

“…Dong et al [38] demonstrated, through in vitro studies using A549 non-small cell lung cancer cell lines, that serum starvation increases E-cadherin expression. E-cadherin is involved in the pathobiology of several types of cancer: the loss or dysfunction of E-cadherin is associated with increased lung cancer cell proliferation and invasiveness [39].…”

Section: Dietary Restriction-induced Molecular Changesmentioning

confidence: 99%

Dietary restriction: could it be considered as speed bump on tumor progression road?

et al. 2016

View full text Add to dashboard Cite

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long-and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models.However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes.

show abstract

Serum starvation regulates E-cadherin upregulation via activation of c-Src in non-small-cell lung cancer A549 cells

Cited by 21 publications

References 55 publications

The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E‐cadherin‐mediated adherens junctions

The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E‐cadherin‐mediated adherens junctions

Silencing Akt1 Inhibits Starvation Induced Lung Metastasis Through Epithelial Mesenchymal Transition Independent of E-cadherin in Prostate Cancer

Dietary restriction: could it be considered as speed bump on tumor progression road?

Contact Info

Product

Resources

About