Bone morphogenetic protein receptor 1α promotes osteolytic lesion of oral squamous cell carcinoma by SHH-dependent osteoclastogenesis

Cancer Sci. 2022 May;113(5):1639-1651. doi: 10.1111/cas.15330. Epub 2022 Mar 23.


Oral squamous cell carcinoma (OSCC) is an aggressive tumor that usually invades the maxilla or mandible. The extent and pattern of mandibular bone invasion caused by OSCC are the most important factors determining the treatment plan and patients' prognosis. Yet, the process of mandibular invasion is not fully understood. The following study explores the molecular mechanism that regulates the mandibular invasion of OSCC by focusing on bone morphogenetic protein receptor 1α (BMPR1α) and Sonic hedgehog (SHH) signals. We found that BMPR1α was positively correlated to bone defect of OSCC patients. Mechanistically, BMPR1α signaling regulated the differentiation and resorption activity of osteoclasts through the interaction of OSCC cells and osteoclast progenitors, and this process was mediated by SHH secreted by tumor cells. The inhibition of SHH protected bone from tumor-induced osteolytic activity. These results provide a potential new treatment strategy for controlling OSCC from invading the jawbones.

Keywords: bone invasion; bone morphogenetic protein receptor 1α; hedgehog pathway; oral squamous cell carcinoma; tumor-bone microenvironment.

MeSH terms

  • Bone Morphogenetic Protein Receptors
  • Bone Morphogenetic Protein Receptors, Type I / metabolism*
  • Bone Morphogenetic Proteins
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Head and Neck Neoplasms*
  • Hedgehog Proteins / metabolism
  • Humans
  • Mouth Neoplasms* / pathology
  • Osteoclasts
  • Osteogenesis
  • Squamous Cell Carcinoma of Head and Neck


  • Bone Morphogenetic Proteins
  • Hedgehog Proteins
  • SHH protein, human
  • Bone Morphogenetic Protein Receptors
  • Bone Morphogenetic Protein Receptors, Type I