PTCH1 regulates anchorage-independent growth and bone invasion of non-small cell lung cancer cells

Bone. 2021 Mar;144:115829. doi: 10.1016/j.bone.2020.115829. Epub 2020 Dec 29.

Abstract

Acquisition of metastatic potential by cancer cells is related to cancer stemness and anchorage-independent growth. The onset and progression of cancer are known to involve Hedgehog (HH) signaling that is activated by the binding of HH to the Patched 1 (PTCH1) receptor. However, the functions and mechanisms of action of PTCH1 in the context of bone metastasis remain to be elucidated. In this study, lentivirally-delivered shRNA was used to deplete PTCH1 levels, which resulted in the inhibition of spherical colony formation by the human non-small cell lung cancer (NSCLC) cell line; this suggested that PTCH1 promotes anchorage-independent growth. Concordantly, knockdown of PTCH1 resulted in significantly reduced migration and invasion of NSCLC cells; this was accompanied by the downregulation of MMP7 and SOX2. PTCH1 knockdown resulted in decreased bone destruction and osteoclastogenesis in a mouse bone metastasis model. These results indicate that PTCH1 may be an important regulator of bone invasion, and strongly suggest that knockdown of PTCH1 may decrease the anchorage-independent growth and metastatic potential of NSCLC.

Keywords: Anchorage-independent growth; Bone metastasis; Invasion; Lung cancer; PTCH1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Hedgehog Proteins
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mice
  • Patched-1 Receptor* / genetics
  • Patched-1 Receptor* / metabolism
  • Signal Transduction

Substances

  • Hedgehog Proteins
  • PTCH1 protein, human
  • Patched-1 Receptor