SHIP prevents metastasis

Krystal, Gerald; Hamilton, Melisa J.; Bennewith, Kevin L.

doi:10.18632/aging.100964

Cited by 3 publications

(3 citation statements)

References 8 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result, SHIP-1 regulates the activity of numerous signaling pathways, including those involved in cell differentiation, proliferation, apoptosis, mobilization and function of myeloid immune cells [17,23]. Deficiency in SHIP-1 expression results in chronic myeloid leukemia in both humans and mice [24], consistent with studies reporting that SHIP-1 acts as a tumor suppressor preventing metastasis in a pre-clinical lung cancer model [25]. In previous studies, we reported a significant expansion of immunosuppressive macrophages in SHIP-1-deficient mice [26].…”

Section: Introductionsupporting

confidence: 79%

Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer

Villalobos-Ayala

Rivera

Alvarez

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Buy / Rent full text

Pancreatic cancer (PC) has an extremely poor prognosis due to the expansion of immunosuppressive myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in the inflammatory tumor microenvironment (TME), which halts the recruitment of effector immune cells and renders immunotherapy ineffective. Thus, the identification of new molecular targets that can modulate the immunosuppressive TME is warranted for PC intervention. Src Homology-2 (SH2) domain-containing Inositol 5′-Phosphatase-1 (SHIP-1) is a lipid signaling protein and a regulator of myeloid cell development and function. Herein, we used the bioflavonoid apigenin (API) to reduce inflammation in different PC models. Wild type mice harboring heterotopic or orthotopic PC were treated with API, which induced SHIP-1 expression, reduced inflammatory tumor-derived factors (TDF), increased the proportion of tumoricidal macrophages and enhanced anti-tumor immune responses, resulting in a reduction in tumor burden compared to vehicle-treated PC mice. In contrast, SHIP-1-deficient mice exhibited an increased tumor burden and displayed augmented proportions of pro-tumor macrophages. These results provide further support for the importance of SHIP-1 expression in promoting pro-tumor macrophage development in the pancreatic TME. Our findings suggest that agents augmenting SHIP-1 expression may provide novel therapeutic options for the treatment of PC.

show abstract

Section: Introductionsupporting

confidence: 79%

Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer

Villalobos-Ayala

Rivera

Alvarez

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Buy / Rent full text

show abstract

“…The PI3K/PTEN/AKT/mTORC1 pathway is dysregulated in multiple cancers including leukemia and multiple solid cancers. Often components of this and related phospholipid signaling pathways are tumor suppressors [ 124 , 125 ]. Multiple components of the PI3K/PTEN/AKT/mTORC1 pathway have and are being considered for potential targeting in human cancer, e.g., p70S6K in breast cancer [ 126 ], as well as, obesity [ 127 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells

Abrams

Ruvolo

et al. 2017

Oncotarget

View full text Add to dashboard Buy / Rent full text

A critical problem in leukemia as well as other cancer therapies is the development of chemotherapeutic drug-resistance. We have developed models of hematopoietic drug resistance that are based on expression of dominant-negative TP53 [TP53 (DN)] or constitutively-active MEK1 [MEK1(CA)] oncogenes in the presence of chemotherapeutic drugs. In human cancer, functional TP53 activity is often lost in human cancers. Also, activation of the Raf/MEK/ERK pathway frequently occurs due to mutations/amplification of upstream components of this and other interacting pathways. FL5.12 is an interleukin-3 (IL−3) dependent hematopoietic cell line that is sensitive to doxorubicin (a.k.a Adriamycin). FL/Doxo is a derivative cell line that was isolated by culturing the parental FL5.12 cells in doxorubicin for prolonged periods of time. FL/Doxo + TP53 (DN) and FL/Doxo + MEK1 (CA) are FL/Doxo derivate cell lines that were infected with retrovirus encoding TP53 (DN) or MEK1 (CA) and are more resistant to doxorubicin than FL/Doxo cells. This panel of cell lines displayed differences in the sensitivity to inhibitors that suppress mTORC1, BCL2/BCLXL, MEK1 or MDM2 activities, as well as, the proteasomal inhibitor MG132. The expression of key genes involved in cell growth and drug-resistance (e.g., MDM2, MDR1, BAX) also varied in these cells. Thus, we can begin to understand some of the key genes that are involved in the resistance of hematopoietic cells to chemotherapeutic drugs and targeted therapeutics.

show abstract

“…We have also reported the expansion of immunosuppressive M2 macrophage in SHIP-1-deficient mice [ 29 ]. Therefore, SHIP-1 acts as a tumor suppressor, preventing metastasis in pre-clinical cancer models [ 94 ]. In the present study, we are the first to show greater miR-155 expression in the BM and tumors of SHIP KO -HPC mice compared with SHIP WT -HPC mice indicating the role of SHIP-1 as tumor suppressor and miR-155 as an oncogene.…”

Section: Discussionmentioning

confidence: 99%

Apigenin Targets MicroRNA-155, Enhances SHIP-1 Expression, and Augments Anti-Tumor Responses in Pancreatic Cancer

Husain

Villalobos-Ayala²,

Laverde³

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Buy / Rent full text

Pancreatic cancer (PC) is a deadly disease with a grim prognosis. Pancreatic tumor derived factors (TDF) contribute to the induction of an immunosuppressive tumor microenvironment (TME) that impedes the effectiveness of immunotherapy. PC-induced microRNA-155 (miRNA-155) represses expression of Src homology 2 (SH2) domain-containing Inositol 5′-phosphatase-1 (SHIP-1), a regulator of myeloid cell development and function, thus impacting anti-tumor immunity. We recently reported that the bioflavonoid apigenin (API) increased SHIP-1 expression which correlated with the expansion of tumoricidal macrophages (TAM) and improved anti-tumor immune responses in the TME of mice with PC. We now show that API transcriptionally regulates SHIP-1 expression via the suppression of miRNA-155, impacting anti-tumor immune responses in the bone marrow (BM) and TME of mice with PC. We discovered that API reduced miRNA-155 in the PC milieu, which induced SHIP-1 expression. This promoted the restoration of myelopoiesis and increased anti-tumor immune responses in the TME of heterotopic, orthotopic and transgenic SHIP-1 knockout preclinical mouse models of PC. Our results suggest that manipulating SHIP-1 through miR-155 may assist in augmenting anti-tumor immune responses and aid in the therapeutic intervention of PC.

show abstract

SHIP prevents metastasis

Cited by 3 publications

References 8 publications

Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer

Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer

Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells

Apigenin Targets MicroRNA-155, Enhances SHIP-1 Expression, and Augments Anti-Tumor Responses in Pancreatic Cancer

Contact Info

Product

Resources

About