PITX1 facilitates the proliferation and tumorigenesis of NSCLC cells via potentiating PHB2-mediated AKT activity.

Authors

Li Lei, Yang Bo, Duan Shaoxian

Published in

Cellular signalling. Pages 112883. Sep 12, 2026. Epub Sep 12, 2026.

Abstract

Accumulating evidence has revealed that upregulation of paired like homeodomain 1 (PITX1) drives the malignant progression of human cancers. Nevertheless, the role and downstream effector of PITX1 in non-small cell lung cancer (NSCLC) are poorly understood. We investigated the clinical relevance, biological function and mechanism of PITX1 in NSCLC. PITX1 was markedly upregulated in NSCLC tissues, and high PITX1 levels were correlated with the advanced stages and poorer survival of NSCLC. PITX1 overexpression facilitated the proliferative, migration and invasion capacity of NSCLC cells, while knockdown of PITX1 had opposite effect. Dual-luciferase reporter and ChIP-qPCR assays indicated that PITX1 directly bound to the prohibitin 2 (PHB2) promoter region, thereby potentiating its transcriptional activity. We also demonstrated that TAATCC in PHB2 gene promoter was the binding sequences of PITX1. In vitro and in vivo assays revealed that PITX1 overexpression enhanced the proliferation, migration, invasion and tumorigenesis of NSCLC cells, while silencing PHB2 effectively reversed this oncogenic phenotype. Moreover, PITX1 activated AKT signaling via upregulation of PHB2. Inhibition of AKT significantly recued the malignancy of NSCLC cells with overexpression of PITX1. A positive expression correlation between PITX1 and PHB2 was observed in NSCLC, and high expression of either gene predicted unfavorable prognosis. Collectively, this study illustrates that PITX1 exerts oncogenic effects in NSCLC by activating PHB2/AKT axis. Targeting PHB2 may represent a promising direction for further investigation in NSCLC patients with high PITX1 expression, though the clinical efficacy of this approach requires confirmation through additional studies.

PMID:
42731741
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.

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