TGF-β mediated drug resistance in solid cancer

Turati, Marta; Mousset, Alexandra; Issa, Nervana; Turtoï, Andrei; Ronca, Roberto

doi:10.1016/j.cytogfr.2023.04.001

Cited by 14 publications

(3 citation statements)

References 105 publications

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“…As reported in previous studies, CAFs and TGF-β signaling pathway are involved in chemotherapy resistance in a variety of tumors [ 30 , 31 ]. Chemotherapy regimens based on CDDP are commonly indicated as therapeutic interventions for individuals diagnosed with advanced GC [ 3 ].…”

Section: Resultsmentioning

confidence: 81%

Cancer associated fibroblasts-derived SULF1 promotes gastric cancer metastasis and CDDP resistance through the TGFBR3-mediated TGF-β signaling pathway

Fang,

Chen,

Yang

et al. 2024

Cell Death Discov.

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SULF1 has been implicated in a number of malignancies. The function of SULF1 in gastric cancer is disputed. The objective of this study was to examine the role and underlying molecular mechanisms of SULF1 in the context of gastric cancer. We found that the expression of SULF1 was increased in gastric cancer, especially in cancer-associated fibroblasts. The overexpression of SULF1 was found to be significantly correlated with unfavorable prognosis among individuals diagnosed with gastric cancer. Functionally, cancer-associated fibroblasts-derived SULF1 served as a oncogenic molecule which facilitated gastric cancer cells metastasis and CDDP resistance. Mechanistically, SULF1 regulated the communication between gastric cancer cells and cancer-associated fibroblasts in tumor microenvironment as a signaling molecule. Cancer-associated fibroblasts-secreted SULF1 interfered with the interaction between TGF-β1 and TGFBR3 by combining with TGFBR3 on gastric cancer cell membrane, subsequently activated TGF-β signaling pathway. In conclusion, our findings have presented novel approaches for potential treatment and prognosis prediction in individuals diagnosed with gastric cancer through the targeting of the CAFs-SULF1-TGFBR3-TGF-β1 signaling axis.

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Section: Resultsmentioning

confidence: 81%

Cancer associated fibroblasts-derived SULF1 promotes gastric cancer metastasis and CDDP resistance through the TGFBR3-mediated TGF-β signaling pathway

Fang,

Chen,

Yang

et al. 2024

Cell Death Discov.

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“…TGF-β signaling plays a significant role in mediating drug resistance in various cancers via actions on the expression of drug efflux transporters, alteration of cell cycle checkpoints, and modulation of apoptosis pathways, all which can reduce the efficacy of anticancer drugs [ 31 – 35 ]. TGF-β signaling has been linked to the development of resistance to chemotherapy and targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

TGF-β signaling: critical nexus of fibrogenesis and cancer

Giarratana,

Prendergast,

Salvatore

et al. 2024

J Transl Med

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The transforming growth factor-beta (TGF-β) signaling pathway is a vital regulator of cell proliferation, differentiation, apoptosis, and extracellular matrix production. It functions through canonical SMAD-mediated processes and noncanonical pathways involving MAPK cascades, PI3K/AKT, Rho-like GTPases, and NF-κB signaling. This intricate signaling system is finely tuned by interactions between canonical and noncanonical pathways and plays key roles in both physiologic and pathologic conditions including tissue homeostasis, fibrosis, and cancer progression. TGF-β signaling is known to have paradoxical actions. Under normal physiologic conditions, TGF-β signaling promotes cell quiescence and apoptosis, acting as a tumor suppressor. In contrast, in pathological states such as inflammation and cancer, it triggers processes that facilitate cancer progression and tissue remodeling, thus promoting tumor development and fibrosis. Here, we detail the role that TGF-β plays in cancer and fibrosis and highlight the potential for future theranostics targeting this pathway.

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“…Transforming growth factor‐β1 (TGF‐β1) is a growth factor that contributes to GSCs plasticity [26]. The interaction between TGF‐β and its receptors can trigger both SMAD‐dependent and SMAD‐independent signal transduction [27]. TGF‐β plays a dual role in the progression of cancer, not only inhibiting tumor development from precancerous cells but also promoting tumor metastasis [28].…”

Section: Introductionmentioning

confidence: 99%

SPI1 activates TGF‐β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells

Song,

Zhang,

Wang

et al. 2023

Brain Pathology

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Glioma stem cells (GSCs) exhibit diverse molecular subtypes with the mesenchymal (MES) population representing the most malignant variant. The oncogenic potential of Salmonella pathogenicity island 1 (SPI1), an oncogenic transcription factor, has been established across various human malignancies. In this study, we explored the association between the SPI1 pathway and the MES GSC phenotype. Through comprehensive analysis of the Cancer Genome Atlas and Chinese Glioma Genome Atlas glioma databases, along with patient‐derived GSC cultures, we analyzed SPI1 expression. Using genetic knockdown and overexpression techniques, we assessed the functional impact of SPI1 on GSC MES marker expression, invasion, proliferation, self‐renewal, and sensitivity to radiation in vitro, as well as its influence on tumor formation in vivo. Additionally, we investigated the downstream signaling cascades activated by SPI1. Our findings revealed a positive correlation between elevated SPI1 expression and the MES phenotype, which in turn, correlated with poor survival. SPI1 enhanced GSC MES differentiation, self‐renewal, and radioresistance in vitro, promoting tumorigenicity in vivo. Mechanistically, SPI1 augmented the transcriptional activity of both TGF‐β1 and FKBP12 while activating the non‐canonical PI3K/Akt pathway. Notably, inhibition of TGF‐β1/PI3K/Akt signaling partially attenuated SPI1‐induced GSC MES differentiation and its associated malignant phenotype. Collectively, our results underscore SPI1's role in activating TGF‐β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12, thereby supporting the aggressive MES phenotype of GSCs. Therefore, SPI1 emerges as a potential therapeutic target in glioma treatment.

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TGF-β mediated drug resistance in solid cancer

Cited by 14 publications

References 105 publications

Cancer associated fibroblasts-derived SULF1 promotes gastric cancer metastasis and CDDP resistance through the TGFBR3-mediated TGF-β signaling pathway

Cancer associated fibroblasts-derived SULF1 promotes gastric cancer metastasis and CDDP resistance through the TGFBR3-mediated TGF-β signaling pathway

TGF-β signaling: critical nexus of fibrogenesis and cancer

SPI1 activates TGF‐β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells

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