Evidence map›Paper›PMID 42889284›Full record

ArticleResearch (Washington, D.C.)2026

Obesity-Induced PLPE-PTK6-FASN Feedback Loop Drives Enzalutamide Resistance by Exacerbating Lipid Metabolic Dysregulation in Castration-Resistant Prostate Cancer.

Zhuo Xing, Xuewen Jiang, Banking Shi, Ruilin Liu, Ruijiang Zeng, Shangqing Ren, Zexian Ding, Pingxia Lin, Xin Yang, Jinxiang Wang and 2 more

Abstract read
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In one paragraph

Article in Research (Washington, D.C.), 2026. 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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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Zhuo XingDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xuewen JiangDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Jinan, Shandong, China.
Banking ShiDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Jinan, Shandong, China.
Ruilin LiuDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ruijiang ZengDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shangqing RenRobotic Minimally Invasive Surgery Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Zexian DingDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Pingxia LinDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xin YangDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jinxiang WangDepartment of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
Wenjun MaoDepartment of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, China.
Xin JinDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID https://orcid.org/0000-0001-6461-6005

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Obesity represents an independent risk factor for various malignancies, including prostate cancer. However, how specific lipid metabolites influence enzalutamide sensitivity in castration-resistant prostate cancer (CRPC) remains elusive. Here, we find that obesity is associated with poorer clinical outcomes during enzalutamide treatment. Lipidomic profiling reveals that 1-palmitoyl-2-linoleoyl phosphatidylethanolamine (PLPE) is markedly enriched in tumors from these individuals. Mechanistically, elevated PLPE directly binds to the SH2 domain of protein tyrosine kinase 6 (PTK6), driving its membrane translocation and functional activation. Furthermore, PLPE facilitates PTK6-fatty acid synthase (FASN) interaction, enabling PTK6 to mediate FASN phosphorylation at T976 via dual mechanisms: steric occupancy and kinase cascade amplification. This hyperactivation of FASN exacerbates lipid metabolic dysregulation, ultimately conferring enzalutamide resistance. Importantly, FASN-derived palmitic acid serves as a substrate for further PLPE synthesis, thereby reinforcing PTK6 membrane retention in a positive feedback loop. Collectively, this study identifies a PLPE-PTK6-FASN feedback loop that drives lipid metabolic reprogramming and enzalutamide resistance in CRPC with obesity, highlighting the therapeutic potential of cotargeting lipid metabolism and kinase signaling.

Identifiers

PMID42889284
PMCPMC13669505

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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.