Evidence map›Paper›PMID 38245780›Full record

ArticleCell & bioscience2024

MIIP downregulation drives colorectal cancer progression through inducing peri-cancerous adipose tissue browning.

Qinhao Wang, Yuanyuan Su, Ruiqi Sun, Xin Xiong, Kai Guo, Mengying Wei, Guodong Yang, Yi Ru, Zhengxiang Zhang, Jing Li and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell & bioscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
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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

13 authors at 5 institutions in 1 country.

Qinhao Wang *State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. bcmbwang@fmmu.edu.cn.ORCID http://orcid.org/0000-0003-0430-0572
Yuanyuan Su *State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Ruiqi Sun *State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Xin XiongState Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Kai GuoDepartment of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Mengying WeiState Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Guodong YangState Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Yi RuState Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Zhengxiang ZhangDepartment of Pharmacology, Medical College, Yan'an University, Yan'an, 716000, Shaanxi, China.
Jing LiDepartment of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Jing ZhangKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. School of Medicine, Northwest University, Xi'an, 710069, Shaanxi, China.
Qing QiaoDepartment of General Surgery, Tangdu Hospital, Fourth Military Medical University, No. 569 Xinsi Road, Xi'an, 710038, Shaanxi, China. qqing44@fmmu.edu.cn.
Xia LiState Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. lixia@fmmu.edu.cn.
Air Force Medical University · CNMinistry of Education of the People's Republic of China · CNXijing Hospital · CNYan'an University · CNTang Du Hospital · CN

Funding

Key Research and Development Projects of Shaanxi Province 2023-JC-YB-696Key Research and Development Projects of Shaanxi Province 2023-YBSF-119National Natural Science Foundation of China 81901966National Natural Science Foundation of China 82273004State Key Laboratory of Cancer Biology CBSKL2017Z09State Key Laboratory of Cancer Biology CBSKL2019KF01State Key Laboratory of Cancer Biology CBSKL2022ZZ22
6 · The paper itself

Abstract

backgroundThe enrichment of peri-cancerous adipose tissue is a distinctive feature of colorectal cancer (CRC), accelerating disease progression and worsening prognosis. The communication between tumor cells and adjacent adipocytes plays a crucial role in CRC advancement. However, the precise regulatory mechanisms are largely unknown. This study aims to explore the mechanism of migration and invasion inhibitory protein (MIIP) downregulation in the remodeling of tumor cell-adipocyte communication and its role in promoting CRC.

resultsMIIP expression was found to be decreased in CRC tissues and closely associated with adjacent adipocyte browning. In an in vitro co-culture model, adipocytes treated with MIIP-downregulated tumor supernatant exhibited aggravated browning and lipolysis. This finding was further confirmed in subcutaneously allografted mice co-injected with adipocytes and MIIP-downregulated murine CRC cells. Mechanistically, MIIP interacted with the critical lipid mobilization factor AZGP1 and regulated AZGP1's glycosylation status by interfering with its association with STT3A. MIIP downregulation promoted N-glycosylation and over-secretion of AZGP1 in tumor cells. Subsequently, AZGP1 induced adipocyte browning and lipolysis through the cAMP-PKA pathway, releasing free fatty acids (FFAs) into the microenvironment. These FFAs served as the primary energy source, promoting CRC cell proliferation, invasion, and apoptosis resistance, accompanied by metabolic reprogramming. In a tumor-bearing mouse model, inhibition of β-adrenergic receptor or FFA uptake, combined with oxaliplatin, significantly improved therapeutic efficacy in CRC with abnormal MIIP expression.

conclusionsOur data demonstrate that MIIP plays a regulatory role in the communication between CRC and neighboring adipose tissue by regulating AZGP1 N-glycosylation and secretion. MIIP reduction leads to AZGP1 oversecretion, resulting in adipose browning-induced CRC rapid progression and poor prognosis. Inhibition of β-adrenergic receptor or FFA uptake, combined with oxaliplatin, may represent a promising therapeutic strategy for CRC with aberrant MIIP expression.

Indexed as

Adipose tissue browningAZGP1Colorectal cancerMIIP

Identifiers

PMID38245780
PMCPMC10800076
OpenAlexW4391044397

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LicenceCC BY
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Registered trials

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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.