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TRPC1 inhibits the proliferation and migration of estrogen receptor-positive Breast cancer and gives a better prognosis by inhibiting the PI3K/AKT pathway

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Previous studies have indicated that transient receptor potential (TRP) channels can influence cancer development. The TRPC subfamily consists of seven subtypes, TRPC1 − TRPC7. Interestingly, the expression levels of TRPC1 have been shown to be totally different in different breast cancer cell lines. Nevertheless, the underlying mechanism remains unknown. In this study, we explore the significance of TRPC1 expression in breast cancer.

Methods

Immunohistochemical TRPC1 staining was performed in 278 samples. TRPC1 expression in different breast tissues were examined. Then, the influence of TRPC1 on migration, invasion and proliferation was explored. We analyzed the protein of TRPC1 by Western blot to prove which pathway may be involved in. Finally, we use online database to predict the prognosis of TRPC1 in breast cancer.

Results

Through immunohistochemistry and in vitro experiments, we found that the expression level of TRPC1 was higher in breast cancer cells as compared with that in normal breast epithelial cells. Moreover, the expression level of TRPC1 was different between estrogen receptor-positive (ER +) and -negative (ER −) breast cancer. It was shown that TRPC1 inhibited MCF7 cell proliferation, migration, and invasion in vitro. Western blotting revealed that TRPC1 inhibited the PI3K/AKT pathway and epithelium−mesenchymal transformation, leading to subsequent inhibition of cell proliferation and metastasis. In luminal A and luminal B patients, those with high TRPC1 expression had a better prognosis. On the contrary, in basal-like and triple-negative breast cancer (TNBC) subtypes, patients with high-TRPC1 expression had a worse prognosis.

Conclusions

We confirmed that TRPC1 was high expression in breast cancer. Overexpression of TRPC1 inhibits proliferation and migration of ER + breast cancer and gives a better prognosis by inhibiting PI3K/AKT pathway activation. TRPC1 may be an independent prognostic predictor in breast cancer patients.

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Funding

This work partly supported by the funds from National Natural Science Foundation of China [NO.81602345 (Yong-Qu Zhang)], Science and Technology Planning Project of Guangdong Province, China [NO.2016A020215145 (Xiao-Long Wei)], Science and Technology Planning Project of Shantou, China [NO.190917085269842 (Xiao-Long Wei)], Science and Technology Planning Project of Shantou, China [NO.(2019)62 (Yun-Zhu Zeng)].

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Author notes

  1. Li-Ying Zhang and Yong-Qu Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515031, People’s Republic of China

    Li-Ying Zhang, Yun-Zhu Zeng, Jian-Ling Zhu, Huan Chen & Xiao-Long Wei

  2. Department of Breast Center, Cancer Hospital of Shantou University Medical College, No.7 Raoping Road, shantou, 515031, People’s Republic of China

    Yong-Qu Zhang

  3. Department of Breast-Thyroid-Surgery, Xiang’an Hospital of Xiamen University, 2000 Xiang’an East Road, Xiamen, 361101, People’s Republic of China

    Yong-Qu Zhang

  4. Outpatient Department of Breast Center, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515031, People’s Republic of China

    Li-Juan Liu

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  1. Li-Ying Zhang
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Corresponding authors

Correspondence to Xiao-Long Wei or Li-Juan Liu.

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The authors declare that they have no competing interests.

Ethical approval

The work was conducted in accordance with the Declaration of Helsinki. The study was approved by Medical Ethics Committee of the Cancer Hospital of Shantou University Medical College.

Informed consent

This article does not contain any studies with human participants or animals. The entire study protocol was approved by the Medical Ethical Committee of the Cancer Hospital of Shantou University Medical College. The need for obtaining informed consent was waived by this committee.

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Zhang, LY., Zhang, YQ., Zeng, YZ. et al. TRPC1 inhibits the proliferation and migration of estrogen receptor-positive Breast cancer and gives a better prognosis by inhibiting the PI3K/AKT pathway. Breast Cancer Res Treat 182, 21–33 (2020). https://doi.org/10.1007/s10549-020-05673-8

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  • DOI: https://doi.org/10.1007/s10549-020-05673-8

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