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Dive into the research topics where Shelly Tartakover-Matalon is active.

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Featured researches published by Shelly Tartakover-Matalon.


Laboratory Investigation | 2012

Bevacizumab attenuates major signaling cascades and eIF4E translation initiation factor in multiple myeloma cells

Oshrat Attar-Schneider; Liat Drucker; Victoria Zismanov; Shelly Tartakover-Matalon; Gloria Rashid; Michael Lishner

Multiple myeloma (MM), a malignancy of plasma cells, remains fatal despite introduction of novel therapies, partially due to humoral factors, including vascular endothelial growth factor (VEGF), in their microenvironment. The aim of this study was to explore the efficacy of anti-VEGF treatment with bevacizumab directly on MM cells. Particular attention was directed to the affect of VEGF inhibition on protein translation initiation. Experiments were conducted on MM cells (lines, bone marrow (BM) samples) cultured on plastic. Inhibition of VEGF was achieved with the clinically employed anti-VEGF antibody, bevacizumab, as a platform and its consequences on viability, proliferation, and survival was assessed. VEGF downstream signals of established importance to MM cell biology were assayed as well, with particular emphasis on translation initiation factor eIF4E. We showed that blocking VEGF is deleterious to the MM cells and causes cytostasis. This was evidenced in MM cell lines, as well as in primary BM samples (BM MM). A common bevacizumab-induced attenuation of critical signaling effectors was determined: VEGFR1, mTOR, c-Myc, Akt, STAT3, (cell lines) and eIF4E translation initiation factor (lines and BM). ERK1/2 displayed a variegated response to bevacizumab (lines). Utilizing a constitutively Akt-expressing MM model, we showed that the effect of bevacizumab on viability and eIF4E status is Akt-dependent. Of note, the effect of bevacizumab was achieved with high concentrations (2 mg/ml), but was shown to be specific. These findings demonstrate that bevacizumab has a direct influence on major pathways critically activated in MM that is independent from its established effect on angiogenesis. The cytostatic effect of VEGF inhibition on MM cells underscores its potential in combined therapy, and our findings, regarding its influence on translation initiation, suggest that drugs that unbalance cellular proteostasis may be particularly effective.


Clinical & Experimental Metastasis | 2014

Placenta-breast cancer cell interactions promote cancer cell epithelial mesenchymal transition via TGFβ/JNK pathway

Shelly Tartakover-Matalon; Liat Drucker; Metsada Pasmanik-Chor; M. Pomeranz; Ami Fishman; Michael Lishner

Women diagnosed with pregnancy associated breast cancer often have advanced cancer with metastases and reduced expression of ERα compared to non-pregnant women. Nevertheless, metastases to the placenta are uncommon. Previously, we demonstrated that breast cancer cells (MCF-7/T47D) migrated from ex vivo human placental explant implantation sites. We aimed to analyze the effect of factors produced during placental implantation or as a result of the interaction between the implanted placentae to cancer cells on cancer cells migration and aggressiveness. We collected supernatants from implanted placentae and placental-breast cancer cells cocultures and analyzed their effects on cancer cells phenotype and pathways. Supernatants collected from breast cancer cells served as controls. We found that supernatants collected from implanted placentae induced modest cancer cells migration that was not accompanied by epithelial to mesenchymal transition (EMT), supported breast cancer cells survival and elevated MCF-7 cell number. The coculture supernatant induced excessive motility and EMT of the MCF-7 cells. This EMT was mediated by Smad3 and JNK/ERK activation. Both placenta and coculture supernatants reduced ERα expression in the cancer cells. Finally, we showed that MCF-7 cocultured with the human placental explants underwent continuous activation of JNK and Smad3 pathways and the EMT process, which led to their migration away from the placental implantation sites. These findings may explain the reduced ERα and elevated metastases found in breast cancer during pregnancy and highlights pathways involved in it.


Molecular Carcinogenesis | 2016

Multiple myeloma and bone marrow mesenchymal stem cells’ crosstalk: Effect on translation initiation

Oshrat Attar-Schneider; Victoria Zismanov; Mahmoud Dabbah; Shelly Tartakover-Matalon; Liat Drucker; Michael Lishner

Multiple myeloma (MM) malignant plasma cells reside in the bone marrow (BM) and convert it into a specialized pre‐neoplastic niche that promotes the proliferation and survival of the cancer cells. BM resident mesenchymal stem cells (BM‐MSCs) are altered in MM and in vitro studies indicate their transformation by MM proximity is within hours. The response time frame suggested that protein translation may be implicated. Thus, we assembled a co‐culture model of MM cell lines with MSCs from normal donors (ND) and MM patients to test our hypothesis. The cell lines (U266, ARP‐1) and BM‐MSCs (ND, MM) were harvested separately after 72 h of co‐culture and assayed for proliferation, death, levels of major translation initiation factors (eIF4E, eIF4GI), their targets, and regulators. Significant changes were observed: BM‐MSCs (ND and MM) co‐cultured with MM cell lines displayed elevated proliferation and death as well as increased expression/activity of eIF4E/eIF4GI; MM cell lines co‐cultured with MM‐MSCs also displayed higher proliferation and death rates coupled with augmented translation initiation factors; in contrast, MM cell lines co‐cultured with ND‐MSCs did not display elevated proliferation only death and had no changes in eIF4GI levels/activity. eIF4E expression was increased in one of the cell lines. Our study demonstrates that there is direct dialogue between the MM and BM‐MSCs populations that includes translation initiation manipulation and critically affects cell fate. Future research should be aimed at identifying therapeutic targets that may be used to minimize the collateral damage to the cancer microenvironment and limit its recruitment into the malignant process.


Molecular Carcinogenesis | 2017

First trimester human placenta prevents breast cancer cell attachment to the matrix: The role of extracellular matrix.

Liat Drucker; M. Pomeranz; Ami Fishman; Metsada Pasmanik-Chor; Shelly Tartakover-Matalon; Michael Lishner

The extracellular matrix (ECM) affects cancer cell characteristics. Its detachment from the ECM induces cell apoptosis, termed anoikis. Cancer cells can develop anoikis resistance, a necessary step for metastasis, by switching integrins, over‐expressing growth factor receptors, and inducing epithelial mesenchymal transition (EMT). The placenta is a non‐supportive microenvironment for cancer cells. We showed that breast cancer cells (BCCL) were eliminated from placental implantation sites. During implantation, the placenta manipulates its surrounding matrix, which may induce BCCL elimination. Here, we explored the effect of placenta‐induced ECM manipulations on BCCL. During experiments, BCCL (MCF‐7/T47D) were cultured on placenta/BCCL‐conditioned ECM (Matrigel used for first trimester placenta/BCCL culture and cleared by NH4OH). After culturing the cells, we analyzed cancer cell phenotype (death, count, aggregation, MMP) and signaling (microarray analysis and pathway validation). We found that the BCCL did not attach to previous placental implantation sites and instead, similarly to anoikis‐resistant cells, migrated away, displayed increased MMP levels/activity, and formed aggregates in distant areas. T47D were less affected than the MCF‐7 cells, since MCF‐7 also showed modest increases in cell death, EMT, and increased proliferation. Microarray analysis of the MCF‐7 highlighted changes in the integrin, estrogen, EGFR, and TGFβ pathways. Indeed, placental ECM reduced ERα, induced Smad3/JNK phosphorylation and increased integrin‐α5 expression (RGD‐dependent integrin) in the BCCL. Addition of RGD or TGFβR/JNK inhibitors reversed the phenotypic changes. This study helps explain the absence of metastases to the placenta and why advanced cancer is found in pregnancy, and provides possible therapeutic targets for anoikis‐resistant cells.


Human Reproduction | 2005

Simvastatin has deleterious effects on human first trimester placental explants

I. Kenis; Shelly Tartakover-Matalon; N. Cherepnin; Liat Drucker; Ami Fishman; M. Pomeranz; Michael Lishner


Carcinogenesis | 2006

Promoter hypermethylation of tetraspanin members contributes to their silencing in myeloma cell lines

Liat Drucker; Tali Tohami; Shelly Tartakover-Matalon; Victoria Zismanov; Hava Shapiro; Judith Radnay; Michael Lishner


Human Reproduction | 2007

Impaired migration of trophoblast cells caused by simvastatin is associated with decreased membrane IGF-I receptor, MMP2 activity and HSP27 expression

Shelly Tartakover-Matalon; N. Cherepnin; M. Kuchuk; Liat Drucker; I. Kenis; Ami Fishman; M. Pomeranz; Michael Lishner


Placenta | 2012

The involvement of eukaryotic translation initiation factor 4E in extravillous trophoblast cell function

E. Kitroser; M. Pomeranz; G. Epstein Shochet; Ami Fishman; Liat Drucker; D. Sadeh-Mestechkin; Michael Lishner; Shelly Tartakover-Matalon


Cellular Signalling | 2008

Tetraspanins affect myeloma cell fate via Akt signaling and FoxO activation

Michael Lishner; Victoria Zismanov; Tali Tohami; Shelly Tartakover-Matalon; Avishay Elis; Liat Drucker


Cellular Signalling | 2014

Targeting eIF4GI translation initiation factor affords an attractive therapeutic strategy in multiple myeloma

Oshrat Attar-Schneider; Liat Drucker; Victoria Zismanov; Shelly Tartakover-Matalon; Michael Lishner

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