Study identifies SLC38A7 as a driver of gastric cancer growth through the MYH9–Wnt/β-catenin axis

Gastric cancer remains one of the world’s leading causes of cancer-related death, and outcomes for advanced disease are still poor despite progress in diagnosis and treatment. One reason is that gastric cancer is molecularly heterogeneous, which makes it difficult to identify broadly useful therapeutic targets. In a new study published in the journal Chinese Medical Journal on April 14, 2026, researchers report that the lysosomal amino acid transporter SLC38A7 may be one such target. Their work shows that SLC38A7 is not only elevated in gastric cancer but also actively drives tumor growth and spread through a signaling pathway linked to nutrient stress.

The team first analyzed public transcriptomic datasets and found that SLC38A7 was significantly upregulated in gastric cancer compared with normal gastric tissue. Among members of the SLC38 family, SLC38A7 also showed the strongest diagnostic performance in receiver operating characteristic analysis. Higher SLC38A7 expression was associated with shorter overall survival, first progression, and post-progression survival. The researchers then validated these findings in 60 paired gastric cancer and adjacent nontumor tissue samples collected at the Chinese PLA General Hospital, and confirmed increased expression in multiple gastric cancer cell lines.

Functionally, SLC38A7 behaved as an oncogenic factor. In gain- and loss-of-function experiments, silencing SLC38A7 suppressed gastric cancer cell proliferation, migration, and invasion, whereas overexpression produced the opposite effects. These tumor-promoting effects became especially apparent under glutamine-deprived conditions. That observation is biologically important because SLC38A7 is a lysosome-localized glutamine transporter, suggesting that gastric cancer cells may use it to adapt to metabolic stress in the tumor microenvironment.

To understand how SLC38A7 exerts these effects, the investigators combined gene set enrichment analysis, co-immunoprecipitation, mass spectrometry, structural modeling, site-directed mutagenesis, and ubiquitination assays. Their results point to a specific mechanism: SLC38A7 binds to MYH9 and, through this interaction, promotes ubiquitination and degradation of GSK-3β. Because GSK-3β is a key negative regulator of the Wnt/β-catenin pathway, its destabilization leads to β-catenin accumulation and activation of downstream targets associated with proliferation and malignant progression. The authors further showed that mutating key SLC38A7 residues, especially E12, weakened the interaction with MYH9 and reduced downstream pathway activation.

The biological relevance of this mechanism was supported in several ways. Pharmacologic inhibition of GSK-3β partially rescued the impaired proliferation and migration caused by SLC38A7 knockdown, consistent with the proposed signaling model. In mouse xenograft experiments, tumors derived from SLC38A7-silenced cells grew more slowly and were smaller than controls, while SLC38A7 overexpression enhanced tumor growth. Taken together, the data identify a metabolically sensitive SLC38A7–MYH9–GSK-3β–Wnt/β-catenin axis that helps explain how gastric cancer cells maintain malignant behavior under nutrient-limited conditions.

The study adds a new layer to the current understanding of the interplay between tumor metabolism and oncogenic signaling. It also highlights SLC38A7 as a candidate biomarker and a possible therapeutic target. The authors note that no direct inhibitors of SLC38A7 are currently available, but their findings provide a rationale for future strategies aimed at disrupting the SLC38A7–MYH9 interaction or combining metabolic therapies with Wnt-pathway inhibition. Further work will be needed to define the upstream regulators of SLC38A7 and to test whether this mechanism is shared across other glutamine-dependent cancers.

Reference

Title of original paper: SLC38A7 promotes gastric cancer progression through activating Wnt/β-catenin signaling via interaction with MYH9

Journal: Chinese Medical Journal

DOI: https://doi.org/10.1097/cm9.0000000000004090

About The First Medical Center of Chinese PLA General Hospital, China

The First Medical Center of the Chinese People’s Liberation Army (PLA) General Hospital, also known as the main campus of 301 Hospital, is a leading Grade III Class A comprehensive hospital in Beijing, China. Founded within the PLA General Hospital system, it serves as a major center for clinical care, biomedical research, and medical education. The hospital provides advanced diagnosis and treatment across numerous specialties, supports military and civilian healthcare, and is recognized nationally for managing complex diseases, emergency care, and innovative medical technologies while training future healthcare professionals nationwide.
Website: http://www.301hospital.com.cn/index.html

About Prof. Zhanyu Yang from The First Medical Center of Chinese PLA General Hospital, China
Prof. Zhanyu Yang is a Chief Physician, Professor, and PhD Supervisor. He has led seven research projects funded by the National Natural Science Foundation of China and provincial- or ministerial-level agencies, and has published more than 70 academic papers, including 28 as first or corresponding author. He has received one Second Prize of the National Science and Technology Progress Award, two First Prizes for Military Medical Achievements, and one First Prize of the Chongqing Science and Technology Progress Award. He currently holds multiple academic positions, including member of the Organ Transplantation Branch of the Chinese Medical Association.

About Prof. Zhi Qiao from The First Medical Center of Chinese PLA General Hospital, China
Prof. Zhi Qiao is a Chief Physician, Associate Professor, and Master’s Supervisor. He has led five national and provincial-level research projects, including a subproject of the National Key Technology Support Program, a Beijing Municipal Science and Technology Program project, and a general project under the military equipment development program. He has published 12 SCI papers and 13 Chinese core journal papers as first or corresponding author, and has authored or edited five academic books. He received the 2020 Hainan Provincial Science and Technology Progress Award and has participated in the development of nine national expert consensuses. He currently serves in multiple academic roles, including Vice Chair and Secretary-General of the Gastrointestinal Tumor Committee of the Chinese Research Hospital Association.

About Dr. Kai Li from The First Medical Center of Chinese PLA General Hospital, China
Dr. Kai Li is an Attending Physician, MD, and Postdoctoral Researcher. As the second principal investigator, he has participated in a provincial key research project and has also been involved in multiple national, provincial, and municipal research programs. He has published seven Chinese and English academic papers as first author. He was selected for a hospital-level key young talent development program and also serves as a specially appointed lecturer in laparoscopic training.

About Dr.  Shuyang Sun from Beijing Tuberculosis and Thoracic Tumor Research Institute, China
Dr.  Shuyang Sun is an Attending Physician and MD. He has led or participated in multiple research projects, including the Capital’s Funds for Health Improvement and Research, the National 13th Five-Year Military Medicine Innovation Program, and hospital-level incubation projects. He has long been engaged in related clinical and research work, and has been selected for hospital-level Outstanding Young Talent and Distinguished Young Talent programs.