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Glutamate activates the MAPK pathway by inhibiting LPAR1 expression and promotes anlotinib resistance in thyroid cancer

Year: 2025

Type: article

Abstract: OBJECTIVE: To investigate the effects of glutamate on thyroid cancer (TC) cell lines and TC-anlotinib-resistant cell lines and to explore the potential molecular mechanism of glutamate and LPAR1 in promoting anlotinib resistance in TC. METHODS: Glutamate was used to treat TC cell lines and TC-anlotinib-resistant cell lines, and changes in cell function and effects on the expression of LPAR1 and MAPK pathway-related proteins were assessed. In addition, overexpressed-LPAR1. (OE-LPAR1) cell lines were constructed, and OE-LPAR1 and glutamate were combined with TC cell lines and TC-anlotinib-resistant cell lines to explore the interaction between glutamate and LPAR1. Finally, a xenograft tumor model was established in nude mice, and the protein expression of key nodes was detected for further verification. RESULTS: Glutamate promoted the migration, invasion and proliferation of TC cell lines and TC-anlotinib-resistant cell lines, inhibited the expression of LPAR1, and promoted the expression of MAPK pathway-related proteins, whereas OE-LPAR1 had the opposite effect. Furthermore, glutamate promoted the expression of Ki67, inhibited apoptosis, significantly inhibited the expression of LPAR1, and promoted the expression of MAPK pathway-related proteins in a nude mouse xenograft tumor model, whereas OE-LPAR1 significantly inhibited the expression of Ki67 and promoted apoptosis. CONCLUSION: Our study revealed that glutamate promotes the progression of malignant biological behavior in TC cell lines and TC-anlotinib-resistant cell lines. Additionally, glutamate may activate the MAPK pathway by inhibiting the expression of LPAR1, thereby promoting resistance to anlotinib in TC.

Source: Discover Oncology

DOI: 10.1007/s12672-025-02853-0

Authors: Bin Liu, Ying Peng, Yanjun Su, Chang Diao, Liansheng Cha, Ruochuan Cheng

Institutions: Kunming Medical University, First Affiliated Hospital of Kunming Medical University

Language: English

Topic: Thyroid Cancer Diagnosis and Treatment

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,690