Tumor suppression system induces cancer onset

A research group including Researcher Daichi Honda, Associate Professor Misako Okumura (currently Professor at Tohoku University), and Professor Takahiro Chihara of the Graduate School of Integrated Sciences for Life at Hiroshima University, and Professor Toshinori Ando of the Graduate School of Biomedical and Health Sciences at Hiroshima University, as well as RIKEN and the National Institute for Basic Biology, has discovered that the Hippo pathway, known as a tumor suppressor pathway, induces tumor formation in Drosophila epithelial tissue. It was found that cells with an activated Hippo pathway cause neighboring cells to undergo tumorigenesis through intercellular communication, such as the secretion of growth factors and amino acid transport. This is expected to lead to proposals for new cancer therapeutic strategies targeting the Hippo pathway. The results were published in EMBO Reports on May 1.

The Hippo pathway is known to be a tumor "suppressor" pathway that inhibits excessive tissue and organ growth by regulating cell proliferation and apoptosis. In recent years, however, it has been reported that this pathway "promotes" tumor pathways in several types of cancer. This duality posed a major challenge for cancer therapeutic strategies targeting this pathway, but the details remained unknown.

Therefore, the research group used Drosophila to generate cells with an activated Hippo pathway and observed whether tumor formation occurred. Consequently, it was confirmed that tumor formation occurred in the cells surrounding the Hippo-activated cells. This indicated the possibility that these cells function as tumor-promoting centers, triggering tumor formation mediated by intercellular communication.

Next, to investigate how this cellular communication is conducted, they performed a genetic screening. As a result, they discovered two types of intercellular communication driven by Hippo-activated cells.

The first is a pathway in which Hippo-activated cells express and secrete growth factors (Wingless and Spitz) via apoptosis regulatory factors, thereby inducing tumorigenesis in surrounding cells.

The second is a pathway in which amino acid uptake is promoted via amino acid transporters (Sat1 and Sat2), thereby inducing tumor formation. Furthermore, it was clarified that these two pathways act synergistically to strongly induce tumor formation in neighboring cells.

Chihara stated: "This time, a graduate student without preconceived notions carefully observed 'what is happening in the tissue where the Hippo pathway was manipulated,' which led to the discovery of this unexpected phenomenon. This research made me realize once again the importance of honestly observing the cells and tissues in front of us, without being overly trapped by knowledge and common sense. There are still many mysteries regarding the interaction between cancer cells and surrounding cells. We hope to continue our research carefully while listening to the 'voices of cells' in the future."

Journal Information
Publication: EMBO Reports
Title: The Hippo tumor suppressor pathway triggers non-cell autonomous tumorigenesis in Drosophila
DOI: 10.1038/s44319-026-00778-5