Klabukov I, Sulina Y, Baranovskii D. Letter to the Editor: Autophagy related RHEB-CSF1R complex promotes tumor metastasis in pancreatic cancer: Mechanobiological perspective for RHEB-targeted cancer treatment. World J Gastroenterol 2026; 32(35): 119393 [DOI: 10.3748/wjg.119393]
Corresponding Author of This Article
Ilya Klabukov, PhD, Associate Professor, Department of Regenerative Medicine, National Medical Research Radiological Center, 4 Koroleva Street, Obninsk 249036, Kaluzhskaya Oblast’, Russia. ilya.klabukov@gmail.com
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Oncology
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letter
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Klabukov I, Sulina Y, Baranovskii D. Letter to the Editor: Autophagy related RHEB-CSF1R complex promotes tumor metastasis in pancreatic cancer: Mechanobiological perspective for RHEB-targeted cancer treatment. World J Gastroenterol 2026; 32(35): 119393 [DOI: 10.3748/wjg.119393]
World J Gastroenterol. Sep 21, 2026; 32(35): 119393 Published online Sep 21, 2026. doi: 10.3748/wjg.119393
Letter to the Editor: Autophagy related RHEB-CSF1R complex promotes tumor metastasis in pancreatic cancer: Mechanobiological perspective for RHEB-targeted cancer treatment
Ilya Klabukov, Yana Sulina, Denis Baranovskii
Ilya Klabukov, Denis Baranovskii, Department of Regenerative Medicine, National Medical Research Radiological Center, Obninsk 249036, Kaluzhskaya Oblast’, Russia
Ilya Klabukov, Obninsk Institute for Nuclear Power Engineering, National Research Nuclear University MEPhI, Obninsk 249033, Kaluzhskaya Oblast’, Russia
Yana Sulina, Department of Obstetrics, Gynecology and Perinatal Medicine, Sechenov First Moscow State Medical University (Sechenov University), Moscow 119435, Moskva, Russia
Denis Baranovskii, Institute of Systems Biology and Medicine, Russian University of Medicine, Moscow 117997, Moskva, Russia
Author contributions: Klabukov I conceived and designed the research and wrote the letter; Baranovskii D and Sulina Y analyzed the data; Klabukov I revised the letter.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Corresponding author: Ilya Klabukov, PhD, Associate Professor, Department of Regenerative Medicine, National Medical Research Radiological Center, 4 Koroleva Street, Obninsk 249036, Kaluzhskaya Oblast’, Russia. ilya.klabukov@gmail.com
Received: January 26, 2026 Revised: February 18, 2026 Accepted: March 9, 2026 Published online: September 21, 2026 Processing time: 204 Days and 14 Hours
Abstract
We read with great interest the study by Deng et al published in the World Journal of Gastroenterology, which reported that Ras homolog enriched in brain (RHEB) overexpression is associated with reduced survival in patients with pancreatic cancer (PC). The researchers demonstrated that RHEB enhances cancer cell proliferation, migration, and invasion while suppressing autophagy concurrently. This occurs through the upregulation and interaction of colony stimulating factor 1 receptor, which leads to the phosphorylation of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT1), and mammalian target of rapamycin (TOR) signaling components. This cascade was proposed to drive the expression of epithelial-mesenchymal transition markers, thereby promoting metastatic potential. While these findings provide significant mechanistic insight into RHEB-driven tumor progression, an essential consideration remains unaddressed: The impact of PI3K/AKT1/mTOR phosphorylation on tumor cell mechanosensing and its interaction with the extracellular matrix (ECM). Given the central role of ECM remodeling and mechanical cues in PC aggressiveness, future studies should integrate the mechanobiological aspects of PI3K/AKT1/mTOR pathway activation to better elucidate how RHEB modulates tumor behavior within the physical microenvironment. This letter highlights the potential of interlinked molecular signaling, cellular mechanosensing, and tumor ECM properties to find a promising therapy for PC progression.
Core Tip: Ras homolog enriched in brain (RHEB)-driven pathways promote tumor aggressiveness by phosphorylating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin, which influences tumor cell mechanosensing and interaction with the extracellular matrix. Advanced therapeutic strategies for treating solid tumors could target RHEB-mediated signaling.
