Evidence map›Paper›PMID 39937856›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Clear cell renal carcinoma essentially requires CDKL3 for oncogenesis.

Lanjing Ma, Zhongqiu Pang, Haijiao Zhang, Xueling Yang, Shaoqin Zheng, Yi Chen, Weijie Ding, Qing Han, Xi Zhang, Liu Cao and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

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

17 authors.

Lanjing Ma *College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.ORCID 0009-0009-8072-0940
Zhongqiu Pang *College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.ORCID 0009-0000-2693-7289
Haijiao ZhangCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Xueling YangCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Shaoqin ZhengCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Yi ChenDivision of Hematology and Oncology, Department of Medicine, Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York 10032.
Weijie DingCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Qing HanCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Xi ZhangCollege of Sciences, Northeastern University, Shenyang 110004, China.
Liu CaoCollege of Basic Medical Science, China Medical University, Shenyang 110122, China.ORCID 0000-0001-6471-1993
Teng FeiCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Qiang WangDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China.ORCID 0000-0002-8735-8771
Daming GaoState Key Laboratory of Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
Aina HeDepartment of Oncology, the Sixth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200233, China.
Ke-Bang HuDepartment of Urology, The First Hospital of Jilin University, Changchun 130021, China.
Xuexin LiDepartment of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China.ORCID 0000-0001-5824-9720
Ren ShengCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, China.ORCID 0000-0002-2293-8986

Funding

Foundation for Fundamental Research of China N182005006Liaoning Revitalization Talents Program XLYC1807239MOST | National Natural Science Foundation of China (NSFC) 31970721MOST | National Natural Science Foundation of China (NSFC) 81902830MOST | National Natural Science Foundation of China (NSFC) 82173358
6 · The paper itself

Abstract

Clear cell renal cell carcinoma (ccRCC) is the predominant human renal cancer with surging incidence and fatality lately. Hyperactivation of hypoxia-inducible factor (HIF) and mammalian target of rapamycin (mTOR) signaling are the common signatures in ccRCC. Herein, we employed spontaneous ccRCC model to demonstrate the indispensability of an underappreciated Ser/Thr kinase, CDKL3, in the initiation and progression of ccRCC. Ablation of CDKL3 does not affect normal kidney, but abrogates Akt-mTOR hyperactivity and thoroughly prevents the formation and growth of the HIF-agitated ccRCC in vivo. Remarkable clinical correlations also supported the oncogenic role of CDKL3. Mechanism-wise, cytosolic CDKL3 unexpectedly behaves as the adaptor to physically potentiate mTORC2-dependent Akt activation without functioning through kinase activity. And mTORC2 can phosphorylate and stabilize CDKL3 to form a positive feedback loop to sustain the cancer-favored Akt-mTOR overactivation. Together, we revealed the pathological importance and molecular mechanism of CDKL3-mediated Akt-mTOR axis in ccRCC initiation and progression.

Indexed as

CarcinogenesisCarcinoma, Renal CellKidney NeoplasmsAdultAgedAged, 80 and overAnimalsCytosolDisease ProgressionFemaleHumansHypoxia-Inducible Factor 1MaleMechanistic Target of Rapamycin Complex 2MiceMice, Inbred C57BLCDKL3 protein, humanCDKL3 protein, mouseHypoxia-Inducible Factor 1Mechanistic Target of Rapamycin Complex 2MTOR protein, humanmTOR protein, mouseProtein Serine-Threonine KinasesTOR Serine-Threonine KinasesAktccRCCCDKL3mTORoncogene

Identifiers

PMID39937856
PMCPMC11848426

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.