Wnt signaling: a double-edged sword in protecting bone from cancer

Sun, Xun; Li, Kexin; Li, Bai‐Yan; Yokota, Hiroki

doi:10.1007/s00774-022-01363-1

Cited by 3 publications

(4 citation statements)

References 54 publications

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“…The DNA solution was incubated for 10-15 min at room temperature, and the transfection was performed overnight. Based on the available studies [13][14][15][16][17][18][19][20][21], we present three unconventional maxims of cancer cells:…”

Section: Three Unconventional Maximsmentioning

confidence: 99%

Three unconventional maxims in the natural selection of cancer cells: Generation of induced tumor-suppressing cells (iTSCs)

Li¹,

Huo²,

Li³

et al. 2023

Int. J. Biol. Sci.

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Induced tumor-suppressing cells (iTSCs) can be generated from cancer and non-cancer cells. Here, three paradoxical maxims for the action of iTSCs are reviewed: the secretion of tumor-suppressing proteins, their role as a “double-edged” sword, and the elimination of lesser-fit cancer cells. “Super-fit” cancer cells secrete an array of proteins, most of which contribute to enhancing their growth and removing “lesser-fit” cancer cells. These maxims explain the potential dilemma with therapeutic agents since the inhibitory agents tend to promote the synthesis of tumor-promoting proteins. The maxims suggest the possibility of a novel treatment option using cancer-guided evolutionary-fit iTSCs.

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Section: Three Unconventional Maximsmentioning

confidence: 99%

Three unconventional maxims in the natural selection of cancer cells: Generation of induced tumor-suppressing cells (iTSCs)

Li¹,

Huo²,

Li³

et al. 2023

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

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“…A particularly promising route to target Wnt signaling is via the inhibition of their production or secretion by, for example, selectively inhibiting the activity of porcupine (PRCN), a transmembrane protein located in the endoplasmic reticulum. It adds a palmitoyl group to Wnt ligands that is essential for their signaling ability and that is required for the secretion of all Wnt ligands [ 2 , 151 ]. Previous studies showed that PRCN overexpression correlates with Wnt signaling activity in gastric and lung cancers.…”

Section: Therapeutic Opportunities and Future Perspectivesmentioning

confidence: 99%

Wnt Signaling in the Development of Bone Metastasis

Ben-Ghedalia-Peled

Vago

2022

Cells

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Wnt signaling occurs through evolutionarily conserved pathways that affect cellular proliferation and fate decisions during development and tissue maintenance. Alterations in these highly regulated pathways, however, play pivotal roles in various malignancies, promoting cancer initiation, growth and metastasis and the development of drug resistance. The ability of cancer cells to metastasize is the primary cause of cancer mortality. Bone is one of the most frequent sites of metastases that generally arise from breast, prostate, lung, melanoma or kidney cancer. Upon their arrival to the bone, cancer cells can enter a long-term dormancy period, from which they can be reactivated, but can rarely be cured. The activation of Wnt signaling during the bone metastasis process was found to enhance proliferation, induce the epithelial-to-mesenchymal transition, promote the modulation of the extracellular matrix, enhance angiogenesis and immune tolerance and metastasize and thrive in the bone. Due to the complexity of Wnt pathways and of the landscape of this mineralized tissue, Wnt function during metastatic progression within bone is not yet fully understood. Therefore, we believe that a better understanding of these pathways and their roles in the development of bone metastasis could improve our understanding of the disease and may constitute fertile ground for potential therapeutics.

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“…For advanced and metastatic breast cancer, prostate cancer as well as osteosarcoma, an unconventional treatment strategy using “induced tumor-suppressing cells” (iTSCs) has been proposed 12 . iTSCs can be generated from various cell types, including mesenchymal stem cells (MSCs), osteocytes, osteoblasts, and peripheral blood mononuclear cells, as well as breast and prostate cancer cells 13 – 18 . It requires the activation of cell proliferating and oncogenic pathways, for instance, by overexpressing β-catenin in Wnt signaling, and Snail in the epithelial-to-mesenchymal transition 13 .…”

Section: Introductionmentioning

confidence: 99%

“…iTSCs can be generated from various cell types, including mesenchymal stem cells (MSCs), osteocytes, osteoblasts, and peripheral blood mononuclear cells, as well as breast and prostate cancer cells 13 – 18 . It requires the activation of cell proliferating and oncogenic pathways, for instance, by overexpressing β-catenin in Wnt signaling, and Snail in the epithelial-to-mesenchymal transition 13 . Our previous studies have suggested that iTSCs could be generated by transfecting MSCs with Lrp5, β-catenin, Snail, or Akt 12 , 14 , 15 , 19 , 20 .…”

Section: Introductionmentioning

confidence: 99%

The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes

Huo,

Li,

Sun

et al. 2023

Sci Rep

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival. To explore an uncharted function of K-Ras proto-oncogene, K-Ras was activated in mesenchymal stem cells (MSCs) and the effects of MSC conditioned medium (CM) on PDAC were examined. Overexpression of K-Ras elevated PI3K signaling in MSCs, and K-Ras/PI3K-activated MSC-derived CM reduced the proliferation and migration of tumor cells, as well as the growth of ex vivo freshly isolated human PDAC cultures. CM’s anti-tumor capability was additive with Gemcitabine, a commonly used chemotherapeutic drug in the treatment of PDAC. The systemic administration of CM in a mouse model suppressed the colonization of PDAC in the lung. MSC CM was enriched with Moesin (MSN), which acted as an extracellular tumor-suppressing protein by interacting with CD44. Tumor-suppressive CM was also generated by PKA-activated peripheral blood mononuclear cells. Collectively, this study demonstrated that MSC CM can be engineered to act as a tumor-suppressive agent by activating K-Ras and PI3K, and the MSN-CD44 regulatory axis is in part responsible for this potential unconventional option in the treatment of PDAC.

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Wnt signaling: a double-edged sword in protecting bone from cancer

Cited by 3 publications

References 54 publications

Three unconventional maxims in the natural selection of cancer cells: Generation of induced tumor-suppressing cells (iTSCs)

Three unconventional maxims in the natural selection of cancer cells: Generation of induced tumor-suppressing cells (iTSCs)

Wnt Signaling in the Development of Bone Metastasis

The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes

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