Esophageal Cancer: Discovery of the Mechanisms Involved (Medicine)

Publication in Cell Stem Cell: Researchers from the Free University of Brussels (ULB) discover new mechanisms involved in the development of esophageal metaplasias.

Metaplasia is the replacement of one donated differentiated tissue by another in response to chronic tissue damage. There are several known metaplasias including Barrett’s metaplasia or intestinal metaplasia of the esophagus. In response to chronic acid reflux, the squamous tissue that lines the esophagus may indeed be replaced by another type of tissue and these changes are associated with an increased risk (up to 50 times) of developing adenocarcinoma, a malignant tumor. , esophagus. However, the mechanisms involved in these changes in esophageal cells are still poorly understood.

In a study published in the journal Cell Stem Cell, researchers led by Benjamin Beck, FNRS qualified researcher and WELBIO principal investigator at IRIBHM, Université libre de Bruxelles, Belgium, describe mechanisms involved in the change of cells in the esophagus into metaplastic cells. 

Alizée Vercauteren Drubbel and her colleagues combined cutting-edge molecular biology tools with in vivo models to dissect the mechanisms regulating the transition from one cellular state to another in the esophagus. In collaboration with Prof. Sachiyo Nomura (Tokyo Medical University, Japan), a surgeon specializing in the study of esophageal reflux and metaplasia, they demonstrated that chronic reflux induces the reactivation of the Hedgehog signaling pathway in the esophagus, when the latter was extinct since embryonic development. Reactivation of this pathway in the adult esophagus induces dedifferentiation. The cells of the adult esophagus then look like embryonic cells. Some of these cells still change over time,

“It was really surprising to see cells in the esophagus changing gradually by activating only one signaling pathway,”

said Alizée Vercauteren Drubbel, the first author of this study.

The authors showed that the Hedgehog signaling pathway modifies the differentiation of almost all cells in the esophagus, but only rarely induces the appearance of metaplastic cells. The fact that cells for a time resemble embryonic cells suggests that cells in the esophagus must first dedifferentiate before they can differentiate into something else. The authors were able to demonstrate that this change in cell identity was based on the appearance of a protein called Sox9.

In conclusion, this work highlights the mechanisms modulating cell plasticity which could constitute the initial stages of the appearance of metaplasias in the esophagus. The increased incidence of esophageal cancer (adenocarcinoma) appears to be due to the increased frequency of esophageal metaplasias.

“Fortunately, only a minority of patients with esophageal metaplasia develop cancer. We hope that a better understanding of all the mechanisms involved in the development of esophageal metaplasias as well as their progression to cancer will one day help us identify the patients most at risk, ”

comments Benjamin Beck, the last author of this study.

This work was supported by the FNRS, the Worldwide cancer research, the Foundation Against Cancer and the Wallonia-Brussels Federation. Alizée Vercauteren Drubbel was funded by Télévie. Benjamin Beck is a principal investigator of WELBIO / FNRS at the Free University of Brussels (ULB).

The source of these results is the Cell Stem Cell journal:

Reference: Alizée Vercauteren Drubbel, Sheleya Pirard, Simon Kin, Benjamin Dassy, Anne Lefort, Frédérick Libert, Sachiyo Nomura & Benjamin Beck. Reactivation of the Hedgehog pathway in esophageal progenitors turns on an embryonic-like program to initiate columnar metaplasia

Cell Stem Cell 2021,

Provided by ULB

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