Evidence map›Paper›PMID 34582006›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2021

Beta-Pix-dynamin 2 complex promotes colorectal cancer progression by facilitating membrane dynamics.

Seula Keum, Soo Jung Yang, Esther Park, TaeIn Kang, Jee-Hye Choi, Jangho Jeong, Ye Eun Hwang, Jung-Woong Kim, Dongeun Park, Sangmyung Rhee

Open access · hybridAbstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 51% 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

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. Guanine nucleotide exchange factors and colon neoplasia.Frontiers in cell and developmental biology · 2024
    Review
  4. Review
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

10 authors at 4 institutions in 2 countries.

Seula KeumDepartment of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
Soo Jung YangTranslational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101, USA.
Esther ParkSchool of Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
TaeIn KangSchool of Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Jee-Hye ChoiDepartment of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
Jangho JeongDepartment of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
Ye Eun HwangDepartment of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
Jung-Woong KimDepartment of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
Dongeun ParkSchool of Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Sangmyung RheeDepartment of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea. sangmyung.rhee@cau.ac.kr.ORCID http://orcid.org/0000-0001-9646-8035
Chung-Ang University · KRSeoul National University · KRSangmyung University · KRVirginia Mason Medical Center · US

Funding

Chung-Ang University Chung-Ang University Graduate Research Scholarship in 2018Ministry of Science, ICT and Future Planning NRF-2019R1A4A2001609Ministry of Science, ICT and Future Planning NRF-2020R1A2C2007389
6 · The paper itself

Abstract

purposeSpatiotemporal regulation of cell membrane dynamics is a major process that promotes cancer cell invasion by acting as a driving force for cell migration. Beta-Pix (βPix), a guanine nucleotide exchange factor for Rac1, has been reported to be involved in actin-mediated cellular processes, such as cell migration, by interacting with various proteins. As yet, however, the molecular mechanisms underlying βPix-mediated cancer cell invasion remain unclear.

methodsThe clinical significance of βPix was analyzed in patients with colorectal cancer (CRC) using public clinical databases. Pull-down and immunoprecipitation assays were employed to identify novel binding partners for βPix. Additionally, various cell biological assays including immunocytochemistry and time-lapse video microscopy were performed to assess the effects of βPix on CRC progression. A βPix-SH3 antibody delivery system was used to determine the effects of the βPix-Dyn2 complex in CRC cells.

resultsWe found that the Src homology 3 (SH3) domain of βPix interacts with the proline-rich domain of Dynamin 2 (Dyn2), a large GTPase. The βPix-Dyn2 interaction promoted lamellipodia formation, along with plasma membrane localization of membrane-type 1 matrix metalloproteinase (MT1-MMP). Furthermore, we found that Src kinase-mediated phosphorylation of the tyrosine residue at position 442 of βPix enhanced βPix-Dyn2 complex formation. Disruption of the βPix-Dyn2 complex by βPix-SH3 antibodies targeting intracellular βPix inhibited CRC cell invasion.

conclusionsOur data indicate that spatiotemporal regulation of the Src-βPix-Dyn2 axis is crucial for CRC cell invasion by promoting membrane dynamics and MT1-MMP recruitment into the leading edge. The development of inhibitors that disrupt the βPix-Dyn2 complex may be a useful therapeutic strategy for CRC.

Indexed as

Disease ProgressionAmino Acid SequenceCell Line, TumorCell MembraneCell MovementColorectal NeoplasmsDynamin IIGene Expression Regulation, NeoplasticGoldHEK293 CellsHumansMatrix Metalloproteinase 14Metal NanoparticlesNeoplasm InvasivenessPhosphorylationPhosphotyrosineDynamin IIGoldMatrix Metalloproteinase 14Phosphotyrosinerac1 GTP-Binding ProteinRho Guanine Nucleotide Exchange FactorsRNA, MessengerBeta-PixColorectal cancerCytoskeleton rearrangementDynamin 2MetastasisSrc kinase

Identifiers

PMID34582006
PMCPMC8648671
OpenAlexW3204212466

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.