LHPP-P38 MAPK/ERK-ETS1 Axis Negative Feedback Signaling Restrains Progression in Breast Cancer.

IF 5.7 2区医学 Q1 Medicine

Cancer Science Pub Date : 2025-01-10 DOI:10.1111/cas.16448

Xu Liu, Deyang Yu, Zhen Yu, Sisi Su, Meixia Jiang, Chunbo Zhao

引用次数: 0

Abstract

Invasion and metastasis are major causes of mortality in breast cancer (BRCA) patients. LHPP, known for its tumor-suppressive effects, has an undefined role in BRCA. We found reduced LHPP protein in BRCA tissues, with lower levels correlating with poor patient outcomes. In vitro studies show LHPP inhibits BRCA cell proliferation, migration, invasion, and stemness. In vivo xenograft models support LHPP's role in curbing tumorigenesis and lung metastasis. Mechanistically, LHPP interacts with ERK and P38 MAPK, leading to their dephosphorylation and suppression of the MAPK pathway. We also reveal ETS1, a MAPK effector, repressing LHPP mRNA transcription, suggesting a LHPP-P38 MAPK/ERK-ETS1 negative feedback loop as a key regulatory mechanism in controlling BRCA invasion and metastasis.

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LHPP-P38 MAPK/ERK-ETS1轴负反馈信号抑制乳腺癌进展

侵袭和转移是乳腺癌（BRCA）患者死亡的主要原因。LHPP以其肿瘤抑制作用而闻名，但在BRCA中的作用尚不明确。我们发现BRCA组织中LHPP蛋白减少，低水平与患者预后差相关。体外研究表明，LHPP抑制BRCA细胞的增殖、迁移、侵袭和干性。体内异种移植模型支持LHPP在抑制肿瘤发生和肺转移中的作用。在机制上，LHPP与ERK和P38 MAPK相互作用，导致它们的去磷酸化和抑制MAPK通路。我们还发现MAPK效应物ETS1抑制LHPP mRNA转录，表明LHPP- p38 MAPK/ERK-ETS1负反馈回路是控制BRCA侵袭和转移的关键调控机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Science ONCOLOGY-

CiteScore

9.90

自引率

3.50%

发文量

406

审稿时长

17 weeks

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.