Targeting slug-mediated non-canonical activation of c-Met to overcome chemo-resistance in metastatic ovarian cancer cells

Chang, Ling‐Sai; Hu, Yan; Fu, Yingying; Zhou, Tianyi; You, Jun; Du, Jiamin; Zheng, Lin; Cao, Ji; Ying, Meidan; Dai, Xiaohu; Su, Dan; He, Qiaojun; Zhu, Hong; Yang, Bo

doi:10.1016/j.apsb.2019.03.001

Cited by 25 publications

(15 citation statements)

References 37 publications

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“…Furthermore, mesenchymal markers (i.e., Vimentin or N-Cadherin) decrease the polarity of cancer cells and accelerate migration and invasion 56,57 . Recently, the EMT process has been proposed as an important regulator of drug resistance [58][59][60] . Accumulating data have confirmed that mechanisms of resistance to sorafenib may involve the EMT and the Notch signaling pathway is a key regulator of the EMT process [61][62][63] .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

et al. 2019

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Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial-mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3′-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

et al. 2019

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“…Alternatively, we tested whether SLUG was upstream of ITGB1. This too was plausible since others have reported SLUG to regulate integrins in keratinocytes [ 51 ], wound healing in the gut [ 52 ], and in ovarian cancer cells [ 53 ]. However, SLUG knockdown yielded no change in ITGB1 in our CTC models of HCC and CRPC.…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG

Huaman

Ogunwobi

2020

Cells

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Fibronectin (FN1) is an extracellular matrix protein gaining increasing attention for its multifaceted roles in cancer progression. Using our recently established circulating tumor cell (CTC) lines, we had demonstrated increased FN1 expression and enhanced migration in CTC lines, in comparison to primary tumor cell lines. Whether increased FN1 expression is directly required for CTC migration, and the specific role of FN1’s regulation of integrin B1 (ITGB1) and SLUG (SNAI2) in CTC migration remains unclear. Here, for the first time, we report that the knockdown of FN1, ITGB1, or SLUG expression in CTCs leads to a significant decrease in CTC migration. Knocking down two or all three of these proteins simultaneously did not further inhibit migration. We observed a corresponding increase in CTC migration when recombinant FN1 was added to CTCs. This effect was significantly impeded by prior knockdown of ITGB1 or SLUG. Using knock down experiments and western blotting analysis, we confirmed FN1’s regulation of ITGB1 and SLUG to occur via two separate, independent pathways. Consequently, we can conclude that FN1-dependent enhanced migration of CTCs requires downstream signaling through either ITGB1 or SLUG and that FN1 regulation of ITGB1 and SLUG may have important implications for cancer progression and metastasis.

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“…CAL 27 and SCC-15 cell were seeded onto six-well plates and allowed to form confluent monolayer overnight. Next day, a wound was created by scraping the cell monolayer with 200 μL pipette tip as described previously 33 . The cultures were washed three times with fresh medium to remove debris and treated with varying dilutions of PEP06 (50, 100 and 200 μg/mL) or endostatin (100 μg/mL) for 48 h. The images of wounds were captured for each group at 0 and 48 h, and the gap width was analyzed using Image-Pro Plus 6.0 (Media Cybernetics, Rockville, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting v integrin/FAK/Src signaling in oral squamous cell carcinoma cells

Tuguzbaeva

Yue

Chen

et al. 2019

Acta Pharmaceutica Sinica B

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Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), αv integrin is a crucial mediator of multicellular clustering and collective movement in vitro; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent in vitro. Firstly, we found marked enrichment of αv integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of αv integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed αv integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell–cell contacts contributed to diminished collective migration of OSCC in vitro. Overall, these results suggest that PEP06 polypeptide 30 inhibiting αv integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

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Targeting slug-mediated non-canonical activation of c-Met to overcome chemo-resistance in metastatic ovarian cancer cells

Cited by 25 publications

References 37 publications

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting v integrin/FAK/Src signaling in oral squamous cell carcinoma cells

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