Adipocyte promotes tumor cell invasion and metastasis via FATP2: a novel cell-cell interaction in papillary thyroid carcinoma.

Background: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the endocrine system, with its incidence increasing annually worldwide. Currently, despite the adoption of various treatment modalities, tumor invasion and metastasis constitute critical factors affecting the long-term survival of PTC patients. Adipocytes participate in regulating the malignant biological characteristics of tumor cells. However, the role of adipocytes in PTC carcinogenesis and progression remains poorly understood. Therefore, this study aims to investigate the role of adipocytes in PTC metastasis. Methods: 3T3L1-D cells were treated with differentiation medium to induce differentiation into adipocytes. PTC cells were cultured with adipocytes, and the PTC cell invasion ability was examined by transwell assay. The associated mechanisms were further investigated. Results: Here, we found that the surrounding adipocytes could promote the invasion capacity of PTC cells via FATP2/TR4 signaling, and the inhibition of FATP2 or TR4 expression could reverse the invasion capacity of PTC cells. Furthermore, the preclinical investigation demonstrated that targeting this newly identified signaling with lipofermata (a FATP2-specific inhibitor) suppressed PTC progression. Conclusions: Together, these findings suggest that adipocytes in the PTC microenvironment may function via FATP2/TR4 signaling to regulate PTC progression, and targeting this newly identified adipocyte/FATP2/TR4 signaling axis may facilitate the development of novel therapeutic strategies for PTC.