L1CAM is required for early dissemination of fallopian tube carcinoma precursors to the ovary

Commun Biol. 2022 Dec 12;5(1):1362. doi: 10.1038/s42003-022-04314-8.


Most ovarian high-grade serous carcinomas (HGSC) arise from Serous Tubal Intraepithelial Carcinoma (STIC) lesions in the distal end of the fallopian tube (FT). Formation of STIC lesions from FT secretory cells leads to seeding of the ovarian surface, with rapid tumor dissemination to other abdominal structures thereafter. It remains unclear how nascent malignant cells leave the FT to colonize the ovary. This report provides evidence that the L1 cell adhesion molecule (L1CAM) contributes to the ability of transformed FT secretory cells (FTSEC) to detach from the tube, survive under anchorage-independent conditions, and seed the ovarian surface. L1CAM was highly expressed on the apical cells of STIC lesions and contributed to ovarian colonization by upregulating integrins and fibronectin in malignant cells and activating the AKT and ERK pathways. These changes increased cell survival under ultra-low attachment conditions that mimic transit from the FT to the ovary. To study dissemination to the ovary, we developed a tumor-ovary co-culture model. We showed that L1CAM expression was important for FT cells to invade the ovary as a cohesive group. Our results indicate that in the early stages of HGSC development, transformed FTSECs disseminate from the FT to the ovary in a L1CAM-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cystadenocarcinoma, Serous* / metabolism
  • Fallopian Tube Neoplasms* / metabolism
  • Fallopian Tube Neoplasms* / pathology
  • Fallopian Tubes / metabolism
  • Fallopian Tubes / pathology
  • Female
  • Humans
  • Neural Cell Adhesion Molecule L1* / metabolism
  • Ovarian Neoplasms* / pathology


  • Neural Cell Adhesion Molecule L1