MINDIN-Induced Attenuation of Primary Cilia Activates Parathyroid Hormone Receptor Type I (PTH1R) to Drive Osteomimicry and Bone Tropism in Prostate Cancer.

Authors

Luis Álvarez-Carrión, Paula Lozano-Bustos, Irene Gutiérrez-Rojas, Martina Romeo, Arancha R Gortázar, Verónica Alonso, Juan A Ardura

Published in

BioFactors (Oxford, England). Volume 52. Issue 5. Pages e70164.

Abstract

Advanced prostate cancer metastasizes primarily to bone, a process driven in part by the de novo expression of bone-associated factors (osteomimicry) that enables tumor cells to colonize and thrive in the skeletal environment. During the early stages of tumorigenesis in multiple cancer types, the primary cilium, a non-motile microtubule-based sensory organelle, is lost. However, the causes of primary cilium loss and the consequences of this process for tumor progression are still ill-defined. The aim of this study was to determine whether MINDIN, a protein secreted by prostate tumor cells, promotes primary cilium reduction and osteomimicry, thereby enhancing the ability of prostate cancer cells to colonize bone. We observed that upregulation of MINDIN decreased the levels of the primary cilia marker Ift88 in association with the overexpression of Pth1r, Pthlh, and other osteomimicry-related genes in an in vivo mouse pre-metastatic prostate cancer model. Stimulation with MINDIN decreased primary cilia presence and length and promoted tumor cell osteomimicry, proliferation, and migration; processes similarly induced in primary cilia-inhibited adenocarcinoma prostate cells. Ablation of Pth1r inhibited the effects of both MINDIN and primary cilium loss on prostate cancer cell osteomimicry, proliferation, and migration. Furthermore, Pth1r overexpression and Ift88 downregulation were associated with enhanced tumor cell growth in an ex vivo bone mouse model. Collectively, these findings indicate that MINDIN induces primary cilia attenuation leading to activation of PTH1R, thereby driving osteomimicry and facilitating prostate cancer cell colonization of bone.

PMID:
42902461
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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