Radiation therapy for triple-negative breast cancer: from molecular insights to clinical perspectives

Kim, Jongmyung; Fahmy, Veronia; Haffty, Bruce G.

doi:10.1080/14737140.2024.2333320

Cited by 3 publications

References 47 publications

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FOS‐Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8⁺ T Cells in Triple‐Negative Breast Cancer

Shu,

Lan,

Luo

et al. 2024

Molecular Carcinogenesis

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Radioresistance and immune evasion are interactive and crucial events leading to treatment failure and progression of human malignancies. This research studies the role of phospholipase C beta 1 (PLCB1) in these events in triple‐negative breast cancer (TNBC) and the regulatory mechanism. PLCB1 was bioinformatically predicted as a dysregulated gene potentially linked to radioresistance in TNBC. Parental TNBC cell lines were exposed to fractionated radiation for 6 weeks. PLCB1 expression was decreased in the first 2 weeks but gradually increased from Week 3. PLCB1 knockdown increased the radiosensitivity of the cells, as manifested by a decreased half‐inhibitory dose of irradiation, reduced cell proliferation, apoptosis resistance, mobility, and tumorigenesis in mice. The FOS transcription factor promoted PLCB1 transcription and activated the PI3K/AKT signaling. Knockdown of FOS similarly reduced radioresistance and T cells‐mediated immune evasion. However, the radiosensitivity of TNBC cells and the antitumor effects of CD8+ T cells could be affected by a PI3K/AKT activator or by the PLCB1 upregulation. The PLCB1 or FOS knockdown also suppressed radioresistance and tumorigenesis of the TNBC cells in mice. In conclusion, FOS‐mediated PLCB1 induces radioresistance and weakens the antitumor effects of CD8+ T cells in TNBC by activating the PI3K/AKT signaling pathway.

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FOS‐Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8⁺ T Cells in Triple‐Negative Breast Cancer

Shu,

Lan,

Luo

et al. 2024

Molecular Carcinogenesis

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Transcription Impairment of TMEM208 by ZBTB14 Suppresses Breast cancer Radiotherapy Resistance

Li,

Liang

2024

J Mammary Gland Biol Neoplasia

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Zinc finger and BTB domain-containing protein (ZBTB) proteins have been implicated in different cellular processes, including DNA damage responses and cell cycle progression. However, the mechanism by which ZBTB14 modulates radiotherapy (RT) radioresistance (RT-R) remains to be elucidated. We aimed to elucidate the regulation mechanism of ZBTB14 in breast cancer (BC) RT-R. Using integrated bioinformatics prediction, ZBTB14 was identified as a hub transcription factor related to RT-R in BC. ZBTB14 was significantly under-expressed in non-responders and RT-R/BC cells, whereas its target transmembrane protein 208 (TMEM208) was significantly overexpressed in non-responders and RT-R/BC cells. Chromatin immunoprecipitation-qPCR and luciferase reporter assays revealed that ZBTB14 downregulated TMEM208 expression through transcriptional repression. Overexpression of ZBTB14 significantly inhibited the malignant biological behavior of BC cells and tumor growth in vivo, and further upregulation of TMEM208 reversed the biological activity and radiotherapy resistance of RT-R/BC cells inhibited by overexpression of ZBTB14. Supplementary Information The online version contains supplementary material available at 10.1007/s10911-024-09573-1.

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Induction of cytoplasmic dsDNA and cGAS-STING immune signaling after exposure of breast cancer cells to X-rays or high energetic carbon ions

Totis,

Averbeck,

Jakob

et al. 2024

Preprint

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Radiotherapy can trigger activation of the cGAS-STING axis via cytoplasmic dsDNA fragment induction. The activation of cGAS-STING initiates innate immune signaling mediated by interferon type-I that can contribute to eradicate the malignancy. The effect was shown to depend on the fractionation scheme employed. We hypothesized that the innate immune response can also depend on radiation quality because densely ionizing radiation, such as carbon ions, have different effects on DNA lesion quality. We show here that carbon ions induced a significantly higher yield of cytosolic dsDNA fragments per unit dose as compared to photons in an in vitro 4T1 breast cancer model. The higher efficiency also translated in expression and release of interferon-beta by the tumor cells. Cytoplasmic dsDNA fragments as well as interferon-beta release increased with doses up to 24 Gy and no differences for a fractionation scheme (3x8 Gy) were found as compared to the single high doses of photons. In conclusion, we found that the release of interferon-beta after radiation is increasing with the radiation dose up to 20 Gy and that carbon ions have the potential to elicit a strong innate immune signaling.

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Radiation therapy for triple-negative breast cancer: from molecular insights to clinical perspectives

Cited by 3 publications

References 47 publications

FOS‐Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8⁺ T Cells in Triple‐Negative Breast Cancer

FOS‐Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8⁺ T Cells in Triple‐Negative Breast Cancer

Transcription Impairment of TMEM208 by ZBTB14 Suppresses Breast cancer Radiotherapy Resistance

Induction of cytoplasmic dsDNA and cGAS-STING immune signaling after exposure of breast cancer cells to X-rays or high energetic carbon ions

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Radiation therapy for triple-negative breast cancer: from molecular insights to clinical perspectives

Cited by 3 publications

References 47 publications

FOS‐Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8+ T Cells in Triple‐Negative Breast Cancer

FOS‐Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8+ T Cells in Triple‐Negative Breast Cancer

Transcription Impairment of TMEM208 by ZBTB14 Suppresses Breast cancer Radiotherapy Resistance

Induction of cytoplasmic dsDNA and cGAS-STING immune signaling after exposure of breast cancer cells to X-rays or high energetic carbon ions

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FOS‐Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8⁺ T Cells in Triple‐Negative Breast Cancer

FOS‐Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8⁺ T Cells in Triple‐Negative Breast Cancer