Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK signaling

Sheng, Weiwei; Shi, Xiasheng; Lin, Yiheng; Tang, Jingtong; Chen, Jia; Cao, Rongxian; Sun, Jian; Wang, Guosen; Zhou, Lei; Dong, Ming

doi:10.1186/s13046-020-1521-4

Cited by 92 publications

(69 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ERK signaling pathway will be activated as ROS increases, which finally promote the growth and metastasis of pancreatic cancer [38], therefore we put more attention on the ERK signaling pathway. It has been indicated that ERK signaling pathway can not only promote cell proliferation, apoptosis and metastasis but also induce EMT [39][40][41]. Therefore, we speculated that ABCA8 induces oxidative stress and ROS production through intracellular accumulation of cholesterol, which then induces EMT through the activation of ERK signaling pathway and facilitates the growth and metastasis of HCC cells.…”

Section: Discussionmentioning

confidence: 93%

ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway

Cui

Liang

Zhang

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background: ATP binding cassette subfamily A member 8 (ABCA8) belongs to the ATP binding cassette (ABC) transporter superfamily. ABCA8 is a transmembrane transporter responsible for the transport of organics, such as cholesterol, and drug efflux. Some members of the ABC subfamily, such as ABCA1, may inhibit cancer development. However, the mechanism of ABCA8 in the process of cancer activation is still ambiguous. Methods: The expression of ABCA8 in human hepatocellular carcinoma (HCC) tissues and cell lines was examined using qPCR, immunoblotting, and immunohistochemical staining. The effects of ABCA8 on the proliferation and metastasis of HCC were examined using in vitro and in vivo functional tests. A luciferase reporter assay was performed to explore the binding between microRNA-374b-5p (miR-374b-5p) and the ABCA8 3′-untranslated region (UTR). Results: ABCA8 was frequently down-regulated in HCC and this down-regulation was negatively correlated with prognosis. The overexpression of ABCA8 inhibited growth and metastasis in HCC, whereas the knockdown of ABCA8 exerted the antithetical effects both in vivo and in vitro. ABCA8 was down-regulated by miR-374b-5p; this down-regulation can induce epithelial transformation to mesenchyme via the ERK/ZEB1 signaling pathway and promote HCC progression. Conclusion: We exposed the prognostic value of ABCA8 in HCC, and illuminated a novel pathway in ABCA8regulated inhibition of HCC tumorigenesis and metastasis. These findings may lead to a new targeted therapy for HCC through the regulation of ABCA8, and miR-374b-5p.

show abstract

Section: Discussionmentioning

confidence: 93%

ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway

Cui

Liang

Zhang

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…TGF-β1 activates ERK signaling, which is required for TGF-β1-mediated EMT in vitro 63 . Musashi2 promotes EGFinduced EMT in PC via ZEB1-ERK/MAPK signaling 64 . Taken together, CRT silencing inhibited TG-induced acute ERS and EMT via regulating Slug and ERK signaling in vitro.…”

Section: Discussionmentioning

confidence: 99%

Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress

Sheng

Wang

Tang

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving the oncogenic role of CRT in PC. Methods: We investigated the potential role and mechanism of CRT in regulating intracellular free Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo.Results: Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK). TG-promoted cell invasion and migration was also rescued by CRT silencing but enhanced by IRE1α silencing (one of the key stressors in unfolded protein response). Meanwhile, CRT was co-immunoprecipitated and co-localized with IRE1α in vitro and its silencing led to the chronic ERS via upregulating IRE1α independent of IRE1-XBP1 axis. Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In vivo, CRT silencing decreased subcutaneous tumor size and distant liver metastasis following with the increase of IRE1α expression. A negative relationship between CRT and IRE1α was also observed in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients. Conclusions: CRT promotes EMT in PC via mediating intracellular free Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling.

show abstract

“…Tumor cell invasion and migration are multistep processes which are nely regulated [20][21][22]. The epithelial-to-mesenchymal transition (EMT) has been identi ed as an important process of tumor cell invasion and migration [23][24][25]. Therefore, we determined the effects of PNN on EMT in prostate cancer cell.…”

Section: Pnn Over-expression Induces Prostate Cancer Cell Emtmentioning

confidence: 99%

Pinin promotes tumor progression via PI3K/AKT/CREB signaling pathway in prostate cancer

Meng

Zhang²,

Ren

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background Pinin (PNN), a desmosome associated protein, was demonstrated to be over-expressed and act as a tumor-promoting factor in ovarian cancer, hepatocellular carcinoma and colorectal cancer. However, the precise role of PNN in prostate cancer is still unknown. Methods The expression levels of PNN were assessed in prostate cancer by qRT-PCR, western blotting and immunohistochemical staining. The other proteins were quantified by western blotting. PNN-depleted cells were produced by infecting with lentivirus bearing short hairpin RNAs against PNN. PNN over-expression was performed by transfecting PNN expression vector. The proliferation of each cell line was assessed by MTS and colony formation assays. Tumors were induced on nude mice by injecting tumor cells subcutaneously. Apoptosis and cell cycle were evaluated by flow cytometry. Transwell and wound healing assay were performed to determined the ability of cell invasion and migration. The TCGA data were analyzed with GEPIA (Gene Expression Profiling Interactive Analysis) and GraphPad Prism. Results Here, we reported that PNN was upregulated in prostate cancer tissues and PNN expression was positively associated with Gleason score, tumor stage and tumor metastasis. PNN promoted cell growth and tumorigenicity in vitro and in vivo, and might modulate cell growth through driving G1/S transition via CDK6, CDK2, and Cyclin D1 in prostate cancer cells. Furthermore, PNN accelerated cell invasion, migration and EMT processes of prostate cancer cells accompanied with the up-regulation of MMP-2, MMP-9, N-cadherin, Vimentin and down-regulation of E-cadherin. Mechanism study demonstrated that the proliferation- and motility-promoting effects of PNN on prostate cancer cells dependent on the activation of PI3K/AKT/CREB signaling, which was reversed by AKT and CREB inhibitors. Conclusions Collectively, these findings indicated that PNN plays important roles in prostate cancer tumorigenesis and progression and it may be a potential therapeutic target for prostate cancer treatment.

show abstract

Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK signaling

Cited by 92 publications

References 45 publications

ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway

ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway

Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress

Pinin promotes tumor progression via PI3K/AKT/CREB signaling pathway in prostate cancer

Contact Info

Product

Resources

About