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

Meng,Qingbing; Zhou,Lei; Liang,Haifeng; Hu,Annan; Zhou,Hao; Zhou,Jian; Zhou,Xiaogang; Lin,Hong; Li,Xilei; Jiang,Libo; Dong,Jian

doi:10.3892/ijo.2022.5337

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
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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
Published online on: March 10, 2022 https://doi.org/10.3892/ijo.2022.5337
Article Number: 47
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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