The STAT family: Key transcription factors mediating crosstalk between cancer stem cells and tumor immune microenvironment

Zhu, Min; Li, Suyao; Cao, Xin; Rashid, Khalid; Liu, Tianshu

doi:10.1016/j.semcancer.2022.11.011

Cited by 15 publications

(17 citation statements)

References 132 publications

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“…The JAK/STAT pathway is essential for various cellular functions, including immune responses and inflammation [ 49 ]. JAK is activated by extracellular chemicals, phosphorylating STAT proteins, which in turn alter the nucleus’s gene expression patterns [ 50 ]. This pathway regulates macrophage phenotype and activation.…”

Section: Discussionmentioning

confidence: 99%

SIRPB1 regulates inflammatory factor expression in the glioma microenvironment via SYK: functional and bioinformatics insights

Geng,

Zhao,

et al. 2024

J Transl Med

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Background SIRPB1 expression is upregulated in various tumor types, including gliomas, and is known to contribute to tumor progression; nevertheless, its function in the immune milieu of gliomas is still mainly unknown. Methods This study, we analyzed 1152 normal samples from the GTEx database and 670 glioma samples from the TCGA database to investigate the relationship between the expression of SIRPB1 and clinicopathological features. Moreover, SIRPB1 gene knockout THP-1 cell lines were constructed using CRISPR/Cas9 and were induced into a co-culture of macrophages and glioma cells in vitro to learn more about the role of SIRPB1 in the glioma immune milieu. Lastly, we established a prognostic model to predict the effect of SIRPB1 on prognosis. Results Significantly higher levels of SIRPB1 expression were found in gliomas, which had an adverse effect on the immune milieu and correlated poorly with patient survival. SIRPB1 activation with certain antibodies results in SYK phosphorylation and the subsequent activation of calcium, MAPK, and NF-κB signaling pathways. This phenomenon is primarily observed in myeloid-derived cells as opposed to glioma cells. In vitro co-culture demonstrated that macrophages with SIRPB1 knockout showed decreased IL1RA, CCL2, and IL-8, which were recovered upon ectopic expression of SIRPB1 but reduced again following treatment with SYK inhibitor GS9973. Critically, a lower overall survival rate was linked to increased SIRPB1 expression. Making use of SIRPB1 expression along with additional clinicopathological variables, we established a nomogram that showed a high degree of prediction accuracy. Conclusions Our study demonstrates that glioma cells can be activated by macrophages via SIRPB1, subsequently reprogramming the TME, suggesting that SIRPB1 could serve as a promising therapeutic target for gliomas.

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Section: Discussionmentioning

confidence: 99%

SIRPB1 regulates inflammatory factor expression in the glioma microenvironment via SYK: functional and bioinformatics insights

Geng,

Zhao,

et al. 2024

J Transl Med

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“…This interaction activates the signal transducer and activator of transcription 1 (STAT1) and causes STAT1-promoting cancer stemness. 62 …”

Section: Discussionmentioning

confidence: 99%

Immune system and tumor microenvironment in early-stage breast cancer: different mechanisms for early recurrence after mastectomy and chemotherapy on ductal and lobular types

Andrianto,

Sudiana,

Suprabawati

et al. 2023

F1000Res

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Background: The most common type of breast cancer is the ductal type (IDC), followed by lobular type (ILC). Surgery is the main therapy for early-stage breast cancer. Adjuvant chemotherapy might be given to those at high risk of recurrence. We aimed to determine the mechanisms in early local recurrence in both types. Methods: An observational case-controlled study was used. Early-stage IDC and ILC patients who received modified radical mastectomy (MRM) and adjuvant taxan and anthracycline base chemotherapy had recurrence within two years. We examined vimentin, α-smooth muscle actin (SMA), matrix metalloproteinase (MMP1), platelet-derived growth factor (PDGF), and clustered differentiation (CD95) Results: In the ductal type group, there were 25 samples revealing local recurrence and 25 samples that did not recur. The lobular type group comprised six participants who did not have a recurrence, while seven subjects had a recurrence. There were significant differences in the expression of vimentin (p = 0.000 and 0.021, respectively), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) in ductal and lobular cancer types, respectively. MMP1 (p = 0.000) and α-SMA (p = 0.000) only showed a significant difference in the ductal type. The pathway analysis showed that in the ductal type, the mechanism of recurrence was enabled by two factors: α-SMA and CD95. Meanwhile, for the lobular type, the recurrence mechanism was through the CD95 pathway. Conclusions: The tumor microenvironment and immune system both affect recurrence in IDC, whereas the immune system is more important in ILC. This study suggests that immune system enhancement may be an option for treating cancer.

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“…For example, CAFs could promote tumor stemness through the FGF4–FGF2 axis and high‐mobility group box 1 283,284 . In addition, immune cells in the TME may regulate stemness and self‐renewal of tumor cells via cytokine networks 285,286 …”

Section: Key Molecular Processes In Dtcsmentioning

confidence: 99%

“…283,284 In addition, immune cells in the TME may regulate stemness and self-renewal of tumor cells via cytokine networks. 285,286 It has been confirmed that the TME can promote tumor drug resistance, but the effect of the TME on drug tolerance remains to be unveiled. It has been reported that TKI treatment indirectly induces phenotypic changes in CAFs, which could promote DTC survival through STAT3 activation in lung cancers with EGFR mutations.…”

Section: Tmementioning

confidence: 99%

Targeting drug‐tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells

Song,

Lan,

Zheng

et al. 2023

MedComm

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Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cancer cells could escape intense selective drug treatment by entering a drug‐tolerant state without genetic variations. These drug‐tolerant cells (DTCs) are characterized with a slow proliferation rate and a reversible phenotype. They reside in the tumor region and may serve as a reservoir for resistant phenotypes. The survival of DTCs is regulated by epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions with the tumor microenvironment, and activation of signaling pathways. Thus, targeting the regulators of DTCs opens a new avenue for the treatment of therapy‐resistant tumors. In this review, we first provide an overview of common characteristics of DTCs and the regulating networks in DTCs development. We also discuss the potential therapeutic opportunities to target DTCs. Last, we discuss the current challenges and prospects of the DTC‐targeting approach to overcome acquired drug resistance. Reviewing the latest developments in DTC research could be essential in discovering of methods to eliminate DTCs, which may represent a novel therapeutic strategy for preventing drug resistance in the future.

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The STAT family: Key transcription factors mediating crosstalk between cancer stem cells and tumor immune microenvironment

Cited by 15 publications

References 132 publications

SIRPB1 regulates inflammatory factor expression in the glioma microenvironment via SYK: functional and bioinformatics insights

SIRPB1 regulates inflammatory factor expression in the glioma microenvironment via SYK: functional and bioinformatics insights

Immune system and tumor microenvironment in early-stage breast cancer: different mechanisms for early recurrence after mastectomy and chemotherapy on ductal and lobular types

Targeting drug‐tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells

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