Evidence map›Paper›PMID 41382187›Full record

ArticleEuropean journal of medical research2025

FBXW7 regulates MAP7 through ubiquitination to affect the phenotypic characteristics and paclitaxel sensitivity of paclitaxel-resistant lung adenocarcinoma cells.

Yi Zhang, Jing Xu, Wei Sun, Bingbing Wei, Junwei Zou

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Article in European journal of medical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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5 authors.

Yi ZhangDepartment of Oncology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
Jing XuDepartment of Nursing, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
Wei SunDepartment of Oncology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
Bingbing WeiDepartment of Oncology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
Junwei ZouDepartment of General Surgery, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China. zoujunweimail@163.com.

Funding

the Climbing Scientific Peak Project for Talents, the Second Affiliated Hospital of Wannan Medical College DFJH2022018the Key Project in Natural Science Research in Higher Education Institutions of Anhui Province 2023AH051777the Key project of Natural Science Foundation of Wannan Medical College WK2022ZF29
6 · The paper itself

Abstract

backgroundThe emergence of resistance to paclitaxel (PTX) poses a major challenge to the effective treatment of lung adenocarcinoma (LUAD). This study aimed to elucidate the role of microtubule-associated protein 7 (MAP7) in regulating cell phenotypes and PTX sensitivity of PTX-resistant LUAD cells.

methodsTwo PTX-resistant LUAD cell lines (A549/PTX and HCC-827/PTX) were generated. The effects on cell apoptosis, migration, invasiveness, tube formation, colony formation, and proliferation were evaluated. Subcutaneous xenograft studies were conducted to assess the in vivo role. The regulatory mechanism of F-Box and WD repeat domain containing 7 (FBXW7) on MAP7 protein was examined through stability analysis and immunoprecipitation (IP) assay.

resultsIn PTX-resistant LUAD tumors and cell lines, MAP7 expression was elevated (P < 0.001), while FBXW7 expression was reduced (P < 0.001). Depletion of MAP7 hindered the colony formation (P = 0.0001 or P = 0.0005), invasiveness (P = 0.0004 or P = 0.0005), and migratory capacity (P = 0.0004 or P = 0.001) of A549/PTX and HCC-827/PTX cells. Furthermore, MAP7 overexpression attenuated the anti-cancer effects of PTX in subcutaneous xenograft models (P = 0.0081 or P < 0.001). Mechanistically, FBXW7 destabilized MAP7 protein stability (P < 0.001) by promoting its polyubiquitination at K48. Knockdown of FBXW7 enhanced cell colony formation (P = 0.0029 or P = 0.0007), invasiveness (P = 0.0005 or P < 0.0001), and migration (P = 0.0002 or P < 0.0001) of A549/PTX and HCC-827/PTX cells. Re-expression of MAP7 counteracted (P < 0.01) the inhibitory effects of elevated FBXW7 expression on these cellular processes. In addition, the FBXW7-MAP7 cascade was shown to regulate tube formation in human umbilical vein endothelial cells (HUVECs) (P < 0.01).

conclusionsOur findings indicate that the FBXW7-MAP7 axis plays a critical role in regulating the malignant phenotypes and PTX sensitivity of PTX-resistant LUAD cell lines, suggesting a potential therapeutic strategy to improve the efficacy of PTX-based therapies in LUAD.

Indexed as

Adenocarcinoma of LungDrug Resistance, NeoplasmF-Box-WD Repeat-Containing Protein 7Lung NeoplasmsPaclitaxelA549 CellsAnimalsAntineoplastic Agents, PhytogenicApoptosisCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansMiceMice, NudeAntineoplastic Agents, PhytogenicF-Box-WD Repeat-Containing Protein 7FBXW7 protein, humanPaclitaxelE3-ubiquitin ligaseLung adenocarcinomaMAP7Paclitaxel resistanceUbiquitination

Identifiers

PMID41382187
PMCPMC12696929

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.