Authors
Bo Liu, Yanling Tian, Yang Lv
Published in
Histology and histopathology. Pages 25158. Oct 21, 2026. Epub Oct 21, 2026.
Abstract
Ras-related protein Rab7a participates in fundamental cancer cell processes; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to define Rab7a's oncogenic functions in ESCC and its involvement in the Hippo signaling pathway. Rab7a expression was assessed using ESCC datasets and validated by immunohistochemical analysis of ESCC tissues. We examined functional effects using small interfering RNA knockdown and Yes-associated protein 1 (YAP1) overexpression rescue experiments, primarily by evaluating proliferation, migration, invasion, and apoptosis in ESCC TE-1 cells. We also established a xenograft model for in vivo validation. Regarding its mechanism(s) of action, we analyzed the effects of Rab7a on Hippo core kinases (LATS1/2 and MOB1) and further assessed YAP nuclear localization in ESCC cells. Rab7a was overexpressed in ESCC tissues, and elevated expression correlated with aggressive clinicopathological features, including advanced tumor, node, metastasis stage, positive lymph node metastasis, deep tumor invasion, and poor differentiation. Rab7a knockdown suppressed cellular proliferation, migration, and invasion and induced apoptosis in vitro while inhibiting tumor growth and decreasing Ki-67 expression in vivo. Mechanistically, Rab7a silencing downregulated YAP1, p-YAP1, CTGF, and survivin without affecting MST1. Furthermore, Rab7a knockdown significantly increased p-LATS1/2 levels without altering total LATS1/2 or MOB1 expression and decreased YAP nuclear accumulation. Importantly, YAP1 overexpression effectively reversed the suppressive effects of Rab7a knockdown on malignant phenotypes at both the functional and molecular levels, and restored the expression of downstream targets. Rab7a depletion also reversed an epithelial-mesenchymal transition (EMT)-like phenotype, as evidenced by upregulated E-cadherin and downregulated vimentin and Snail. This effect was rescued by YAP1 overexpression. Our findings demonstrate that Rab7a promotes ESCC progression by regulating the Hippo pathway effector YAP, thus inducing an EMT-like phenotype. Rab7a may serve as a promising prognostic biomarker and therapeutic target in ESCC that functions upstream of LATS1/2 to modulate YAP-mediated tumor progression.
PMID:
42904335
Bibliographic data and abstract were imported from PubMed on 23 Oct 2026.
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