Rapamycin can restore the negative regulatory function of transforming growth factor beta 1 in high grade lymphomas

Sebestyén, Anna; Márk, Ágnes; Hajdú, Melinda; Nagy, Noémi; Molnár, Ágnes; Végsô, Gyula; Barna, Gábor; Kopper, László

doi:10.1016/j.cyto.2015.02.024

Cited by 9 publications

(4 citation statements)

References 38 publications

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“…Surprisingly the role of PP2A in the tumor microenvironment is understudied though some work has been done on PP2A role in TGF beta mediated signaling [203] , [204] , [205] , [206] . TGF beta role in cancer is complex with the molecule demonstrating both tumor suppressor and tumor promoter functions depending on cell type and context [205] , [207] , [208] .…”

Section: Pp2a In the Microenvironmentmentioning

confidence: 99%

“…TGF beta role in cancer is complex with the molecule demonstrating both tumor suppressor and tumor promoter functions depending on cell type and context [205] , [207] , [208] . The cytokine can induce signaling by SMAD-dependent and SMAD-independent pathways with various PP2A family members being involved in both arms [203] , [204] , [205] , [206] . TGF beta-induced SMAD2 phosphorylation is regulated positively by B55 alpha but negatively by B55 delta [203] .…”

Section: Pp2a In the Microenvironmentmentioning

confidence: 99%

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The broken “Off” switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance

2016

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Aberrant activation of signal transduction pathways can transform a normal cell to a malignant one and can impart survival properties that render cancer cells resistant to therapy. A diverse set of cascades have been implicated in various cancers including those mediated by serine/threonine kinases such RAS, PI3K/AKT, and PKC. Signal transduction is a dynamic process involving both “On” and “Off” switches. Activating mutations of RAS or PI3K can be viewed as the switch being stuck in the “On” position resulting in continued signaling by a survival and/or proliferation pathway. On the other hand, inactivation of protein phosphatases such as the PP2A family can be seen as the defective “Off” switch that similarly can activate these pathways. A problem for therapeutic targeting of PP2A is that the enzyme is a hetero-trimer and thus drug targeting involves complex structures. More importantly, since PP2A isoforms generally act as tumor suppressors one would want to activate these enzymes rather than suppress them. The elucidation of the role of cellular inhibitors like SET and CIP2A in cancer suggests that targeting these proteins can have therapeutic efficacy by mechanisms involving PP2A activation. Furthermore, drugs such as FTY-720 can activate PP2A isoforms directly. This review will cover the current state of knowledge of PP2A role as a tumor suppressor in cancer cells and as a mediator of processes that can impact drug resistance and immune surveillance.

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Section: Pp2a In the Microenvironmentmentioning

confidence: 99%

Section: Pp2a In the Microenvironmentmentioning

confidence: 99%

The broken “Off” switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance

2016

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“…The suppressive environment mediated by high TGF-b concentrations affords protection against tumours developing. This happens until carcinogenic cells become resistant to the stimuli initiated by this mediator, for example by the increased activity of mammalian target of rapamycin (mTOR), which makes carcinogenic cells insensitive to TGF-b-mediated antiproliferative activity [35]. In such situations, elevated TGF-b level is beneficial for lymphoma development because it disrupts cytotoxic and proapoptotic activity to tumor-altered cells [33].…”

Section: Immune Response Modulation By H Pylorimentioning

confidence: 99%

The importance of Helicobacter pylori in the development of gastric MALT lymphoma — induction of proliferation and immune suppression

Krzyżek

Kwiatkowska²

2017

Nowotwory. Journal of Oncology

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“…[66]In an Eμ- myc mouse model apoptotic lymphomatous cells stimulated macrophages to produce TGF-β which decelerated lymphoma progression; TGF-β production appears therefore to initially suppress lymphomagenesis. [67] However, acquiring tumor cell resistance to its effects is frequently an important step towards escape.…”

Section: Cytotoxic T Lymphocytes: the Principal Effector Cell In Antimentioning

confidence: 99%

Microenvironment abnormalities and lymphomagenesis: Immunological aspects

Taylor

Gribben

2015

Seminars in Cancer Biology

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Innate and adaptive immune cells within the microenvironment identify and eliminate cells displaying signs of malignant potential. Immunosurveillance effector Natural Killer (NK) cells and Cytotoxic T Lymphocyte (CTLs) identify malignant cells through germline receptors such as NKG2D and in the case of CTLs, presentation of antigen through the T cell receptor. Manipulation of immunosurveillance through altered tumor-identifying ligand expression or secretion, resistance to cytotoxicity, or compromised cytotoxic cell activity through immune tolerance mechanisms all contribute to failure of these systems to prevent cancer development. This review examines the diverse mechanisms by which alterations in the immune microenvironment can promote lymphomagenesis.

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Rapamycin can restore the negative regulatory function of transforming growth factor beta 1 in high grade lymphomas

Cited by 9 publications

References 38 publications

The broken “Off” switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance

The broken “Off” switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance

The importance of Helicobacter pylori in the development of gastric MALT lymphoma — induction of proliferation and immune suppression

Microenvironment abnormalities and lymphomagenesis: Immunological aspects

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