SCYL1-mediated regulation of the mTORC1 signaling pathway inhibits autophagy and promotes gastric cancer metastasis

Sep 21, 2026

Uploaded by Riley

SCYL1-like (SCYL) family proteins have been linked to cancer metastasis, but their gastric cancer (GC) involvement and underlying mechanism remained unclear. This study identified SCYL1’s role in GC using datasets (Deepmap, TCGA, GEO) and validated findings with clinical samples measuring SCYL1 expression and prognosis correlations. Functional assays in vitro and in vivo evaluated GC cell migration, invasion, and autophagy, revealing SCYL1-driven metastatic progression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

Background on GC and metastasis

SCYL family and cancer links

Autophagy and mTORC1 regulation

Materials and methods

Journal of Cancer Research and Clinical Oncology (2024) 150:456 [https://doi.org/10.1007/s00432-024-05938-5](https://doi.org/10.1007/s00432-024-05938-5) SCYL1‑mediated regulation of the mTORC1 signaling pathway inhibits autophagy and promotes gastric cancer metastasis Zihao Zhao1,2,3 · Jinlong Liu1,4 · Xian Gao1,2,3 · Zhuzheng Chen1,2,3 · Yilin Hu1,2,3 · Junjie Chen2,3 · Weijie Zang1,2,3 · Wanjiang Xue1,2,3 Received: 16 July 2024 / Accepted: 2 September 2024 / Published online: 12 October 2024 © The Author(s) 2024 Abstract Background The SCY1-like (SCYL) family has been reported to be closely related to cancer metastasis, but it has not been reported in gastric cancer (GC), and its specific mechanism is not clear. Methods We utilized databases like Deepmap, TCGA, and GEO to identify SCYL1's role in GC. Clinical samples were analyzed for SCYL1 expression and its correlation with patient prognosis. In vitro and in vivo experiments were conducted to assess SCYL1's function in GC cell migration, invasion, and autophagy. Results SCYL1 showed an increased expression in GC tissues, which correlated with a negative prognosis. In vitro experiments demonstrated that SCYL1 promotes GC cell migration and invasion and inhibits autophagy. GSEA indicated an inverse relationship between SCYL1 and autophagy, while a direct relationship was observed with the mTORC1 signaling pathway. Knockdown of SCYL1 enhanced autophagy, while activation of mTORC1 reversed this effect. Conclusions SCYL1 is a significant contributor to GC progression, promoting metastasis by activating the mTORC1 signaling pathway and inhibiting autophagy. These findings suggest SCYL1 as a potential therapeutic target for GC treatment. Keywords SCYL1 · Gastric cancer · Metastasis · mTORC1 · Autophagy Introduction Gastric cancer (GC) ranks among the most common and deadliest types of cancer worldwide. Global cancer statistics indicate that the incidence and mortality rates of GC are significantly high, contributing to the global cancer burden Zihao Zhao, Jinlong Liu and Xian Gao contributed equally to this work. * Wanjiang Xue [xuewanjiang@ntu.edu.cn](xuewanjiang@ntu.edu.cn) Weijie Zang [zangweijie@stmail.ntu.edu.cn](zangweijie@stmail.ntu.edu.cn) 1 Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China 2 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China 3 Nantong Key Laboratory of Gastrointestinal Oncology, Nantong 226001, China 4 Qidong People’s Hospital, Nantong 226001, China (Sung et al. 2020) . Even with the progress in early detection and therapeutic approaches in recent years, the five-year survival rate for GC patients is still under 30%, with some regions reporting even lower percentages. Postoperative recurrence is a major cause of poor prognosis in GC patients, with approximately 60% experiencing varying degrees of recurrence after surgery (Thrift and El-Serag 2020) . This high recurrence rate underscores the urgent need for a deeper understanding of the biology of GC metastasis and the development of new therapeutic strategies to improve long-term patient survival. The SCY1-like (SCYL) family comprises a group of proteins associated with intracellular transport, cell cycle regulation, and signal transduction (Yan et al. 2010). This family includes at least three known members: SCYL1, SCYL2, and SCYL3, all of which possess kinase domains and HEAT repeat sequences (Pelletier 2016) . While the specific roles of their kinase activities in biological functions are not fully understood, they play significant roles in various intracellular processes. The association of the SCYL family with cancer metastasis has been confirmed in multiple studies. For instance, SCYL3 promotes the metastasis of hepatocellular carcinoma by physically binding and regulating the stability and transactivating acti

FAQs

What was the main research question about SCYL1 in gastric cancer?

The study asked whether SCYL1 contributes to gastric cancer progression and clarified how it influences metastasis through autophagy and the mTORC1 signaling pathway.

How were SCYL1’s role and clinical relevance evaluated?

SCYL1 function in GC was assessed using public databases (Deepmap, TCGA, GEO). Clinical samples then measured SCYL1 expression and tested its association with patient prognosis.

What did the experiments show about the relationship between SCYL1, mTORC1, and autophagy?

SCYL1 upregulation correlated with worse prognosis and promoted migration and invasion while inhibiting autophagy. Functional results indicated an inverse relationship between SCYL1 and autophagy and a direct relationship with mTORC1 signaling.

Sep 21, 2026

Uploaded by Riley