Down-regulation of E-cadherin enhances prostate cancer chemoresistance via Notch signaling

Wang, Wenchu; Wang, Lihui; Mizokami, Atsushi; Shi, Jianwu; Zou, Chunlin; Dai, Jinlu; Keller, Evan T.; Lü, Yi; Zhang, Jian

doi:10.1186/s40880-017-0203-x

Cited by 72 publications

(57 citation statements)

References 43 publications

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“…EMT-related transcription factors such as Snail, Slug and Twist are shown to confer chemo-resistance in ovarian, breast and nasopharyngeal carcinoma [ 18 , 19 , 20 ]. In PCa, a study demonstrated that reintroduction of E-cadherin significantly sensitizes chemo-resistant PCa cell lines to paclitaxel [ 21 ]. A recent study showed that Skp2-mediated Twist stabilization can facilitate the acquisition of chemo-resistant to paclitaxel or doxorubicin during PCa progression toward CRPC [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression

Lee

et al. 2017

IJMS

100

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In prostate cancer (PCa), similar to many other cancers, distant organ metastasis symbolizes the beginning of the end disease, which eventually leads to cancer death. Many mechanisms have been identified in this process that can be rationalized into targeted therapy. Among them, epithelial-to-mesenchymal transition (EMT) is originally characterized as a critical step for cell trans-differentiation during embryo development and now recognized in promoting cancer cells invasiveness because of high mobility and migratory abilities of mesenchymal cells once converted from carcinoma cells. Nevertheless, the underlying pathways leading to EMT appear to be very diverse in different cancer types, which certainly represent a challenge for developing effective intervention. In this article, we have carefully reviewed the key factors involved in EMT of PCa with clinical correlation in hope to facilitate the development of new therapeutic strategy that is expected to reduce the disease mortality.

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Section: Introductionmentioning

confidence: 99%

The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression

Lee

et al. 2017

IJMS

100

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“…Many studies have indicated that Snail and E‐cadherin, markers of EMT, induce chemoresistance . Thus, we examined the expression of Snail and E‐cadherin in KYSE70, KYSE70‐siHOXA13, KYSE510, and KYSE510‐HOXA13.…”

Section: Resultsmentioning

confidence: 99%

Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy

et al. 2018

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BackgroundChemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance.MethodsOne hundred thirty‐one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interference was used to knock down the HOXA13 expression in KYSE70 and transfected HOXA13 plasmid to overexpress HOXA13 in KYSE510 cells. We examined half‐maximal inhibitory concentration of cisplatin, apoptosis, and epithelial‐to‐mesenchymal transition (EMT) in ESCC cell lines with different HOXA13 expression levels by cell counting kit‐8, flow cytometry, and transwell analysis.ResultsThe median survival of patients with high HOXA13 expression was significantly shorter than those with low expression (P = 0.027). HOXA13 was associated with worse tumor regression grade (P = 0.009). Low HOXA13 expressed cells decreased the half‐maximal inhibitory concentration of cisplatin (P < 0.05), increased cisplatin‐induced apoptosis (P < 0.05), and decreased EMT (P < 0.05) compared with high HOXA13 expressed cells. In low HOXA13 expressed cells, cleaved caspase‐3 and cleaved PARP expression induced by cisplatin increased, while expression of E‐cadherin and Snail protein, markers of EMT, was upregulated and downregulated, respectively. EMT decreased in low HOXA13 expressed cells.ConclusionHigh HOXA13 expression was associated with inferior tumor regression grade and poor overall survival in ESCC patients treated with neoadjuvant chemotherapy. HOXA13 increased cisplatin‐resistance and promoted EMT in ESCC cells.

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“…This suggests that downregulation of claudin-1 did not affect EMT in prostate epithelial cells. Other studies have shown that claudin-1 overexpression is evident in prostate cancer,30 and that overexpression of E-cadherin (which was not altered by claudin-1 knockdown) downregulated claudin-1 and inhibited tumor cell migration and invasion 31. Our studies suggest that in BPH, which is not associated with prostate carcinogenesis, claudin-1 expression is decreased-and thus our experiments focused on the functional consequences of claudin-1 downregulation and the potential impact of TGF-β1 signaling on the epithelial barrier.…”

mentioning

confidence: 88%

Tight junction protein claudin‐1 is downregulated by TGF‐β1 via MEK signaling in benign prostatic epithelial cells

Wang

Pascal

et al. 2020

The Prostate

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Background Benign prostatic hyperplasia (BPH) is arguably the most common disease in aging men. Although the etiology is not well understood, chronic prostatic inflammation is thought to play an important role in BPH initiation and progression. Our recent studies suggest that the prostatic epithelial barrier is compromised in glandular BPH tissues. The proinflammatory cytokine transforming growth factor beta 1 (TGF‐β1) impacts tight junction formation, enhances epithelial barrier permeability, and suppresses claudin‐1 messenger RNA expression in prostatic epithelial cells. However, the role of claudin‐1 in the prostatic epithelial barrier and its regulation by TGF‐β1 in prostatic epithelial cells are not clear. Methods The expression of claudin‐1 was analyzed in 22 clinical BPH specimens by immunohistochemistry. Human benign prostate epithelial cell lines BPH‐1 and BHPrE1 were treated with TGF‐β1 and transfected with small interfering RNAs specific to claudin‐1. Epithelial monolayer permeability changes in the treated cells were measured using trans‐epithelial electrical resistance (TEER). The expression of claudin‐1, E‐cadherin, N‐cadherin, snail, slug, and activation of mitogen‐activated proteins kinases (MAPKs) and AKT was assessed following TGF‐β1 treatment using Western blot analysis. Results Claudin‐1 expression was decreased in glandular BPH tissue compared with adjacent normal prostatic tissue in patient specimens. TGF‐β1 treatment or claudin‐1 knockdown in prostatic epithelial cell lines increased monolayer permeability. TGF‐β1 decreased levels of claudin‐1 and increased levels of snail and slug as well as increased phosphorylation of the MAPK extracellular signal‐regulated kinase‐1/2 (ERK‐1/2) in both BPH‐1 and BHPrE1 cells. Overexpression of snail or slug had no effect on claudin‐1 expression. In contrast, PD98059 and U0126, inhibitors of the upstream activator of ERK‐1/2 (ie, MEK‐1/2) restored claudin‐1 expression level as well as the epithelial barrier. Conclusion Our findings suggest that downregulation of claudin‐1 by TGF‐β1 acting through the noncanonical MEK‐1/2/ERK‐1/2 pathway triggers increased prostatic epithelial monolayer permeability in vitro. These findings also suggest that elevated TGF‐β1 may contribute to claudin‐1 downregulation and compromised epithelial barrier in clinical BPH specimens.

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Down-regulation of E-cadherin enhances prostate cancer chemoresistance via Notch signaling

Cited by 72 publications

References 43 publications

The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression

The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression

Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy

Tight junction protein claudin‐1 is downregulated by TGF‐β1 via MEK signaling in benign prostatic epithelial cells

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