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Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling

  • Authors:
    • Qingbing Meng
    • Lei Zhou
    • Haifeng Liang
    • Annan Hu
    • Hao Zhou
    • Jian Zhou
    • Xiaogang Zhou
    • Hong Lin
    • Xilei Li
    • Libo Jiang
    • Jian Dong
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Orthopedic Surgery, Xuhui‑Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
    Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 47
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    Published online on: March 10, 2022
       https://doi.org/10.3892/ijo.2022.5337
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Abstract

Estrogen receptor‑positive (ER+) breast cancer (BC) is a malignancy that is prone to metastasis to the spine, which is difficult to treat and often results in poor prognosis. However, the mechanism underlying the tumorigenesis and spinal metastasis of ER+ BC remains unclear. Lysosomal protein transmembrane 5 (LAPTM5) has been reported as a tumor suppressor in several types of cancer, but its role in ER+ BC has not been described. Here, by analyzing a gene sequencing dataset and ER+ BC tissues, tumor‑adjacent normal tissues and spinal metastatic tissues from patients and mouse models, we found that LAPTM5 expression is negatively related to the progression and spinal metastasis of ER+ BC. Subsequently, in vitro experiments demonstrated that downregulation of LAPTM5 expression promoted the proliferation, migration, and chemoresistance of ER+ BC cells by activating glutamine‑dependent mTOR signaling. A high level of CX3CL1 could inhibit LAPTM5 expression, explaining how ER+ BC metastasized to the spine. Thus, we found that LAPTM5 functions as a tumor suppressor in ER+ BC and that the CX3CL/CX3CR1/LAPTM5/glutamine axis mediates the spinal metastasis of ER+ BC. This axis may be a promising therapeutic target for ER+ BC.
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Copy and paste a formatted citation
Spandidos Publications style
Meng Q, Zhou L, Liang H, Hu A, Zhou H, Zhou J, Zhou X, Lin H, Li X, Jiang L, Jiang L, et al: Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling. Int J Oncol 60: 47, 2022.
APA
Meng, Q., Zhou, L., Liang, H., Hu, A., Zhou, H., Zhou, J. ... Dong, J. (2022). Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling. International Journal of Oncology, 60, 47. https://doi.org/10.3892/ijo.2022.5337
MLA
Meng, Q., Zhou, L., Liang, H., Hu, A., Zhou, H., Zhou, J., Zhou, X., Lin, H., Li, X., Jiang, L., Dong, J."Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling". International Journal of Oncology 60.4 (2022): 47.
Chicago
Meng, Q., Zhou, L., Liang, H., Hu, A., Zhou, H., Zhou, J., Zhou, X., Lin, H., Li, X., Jiang, L., Dong, J."Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling". International Journal of Oncology 60, no. 4 (2022): 47. https://doi.org/10.3892/ijo.2022.5337
Copy and paste a formatted citation
x
Spandidos Publications style
Meng Q, Zhou L, Liang H, Hu A, Zhou H, Zhou J, Zhou X, Lin H, Li X, Jiang L, Jiang L, et al: Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling. Int J Oncol 60: 47, 2022.
APA
Meng, Q., Zhou, L., Liang, H., Hu, A., Zhou, H., Zhou, J. ... Dong, J. (2022). Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling. International Journal of Oncology, 60, 47. https://doi.org/10.3892/ijo.2022.5337
MLA
Meng, Q., Zhou, L., Liang, H., Hu, A., Zhou, H., Zhou, J., Zhou, X., Lin, H., Li, X., Jiang, L., Dong, J."Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling". International Journal of Oncology 60.4 (2022): 47.
Chicago
Meng, Q., Zhou, L., Liang, H., Hu, A., Zhou, H., Zhou, J., Zhou, X., Lin, H., Li, X., Jiang, L., Dong, J."Spine‑specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor‑positive breast cancer by activating glutamine‑dependent mTOR signaling". International Journal of Oncology 60, no. 4 (2022): 47. https://doi.org/10.3892/ijo.2022.5337
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