Evidence map›Paper›PMID 42237193›Full record

ArticleCell communication and signaling : CCS2026

Mindin-mediated αM-integrin endocytosis activates STAT3 to maintain keratinocyte stemness.

Binita Dam, Johan Ajnabi, Tirthankar Saha, Ashish Shrivastava, Krithika Badarinath, Akshay Hegde, Abhik Dutta, Siddham Jasoria, Sunny Kataria, Ashutosh Singh and 1 more

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Article in Cell communication and signaling : CCS, 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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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Binita DamInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India.
Johan AjnabiInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India.
Tirthankar SahaInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India.
Ashish ShrivastavaDepartment of Life Sciences, Shiv Nadar Institution of Eminence, NH91, Tehsil Dadri, Greater Noida, Uttar Pradesh , 201314, India.
Krithika BadarinathInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India.
Akshay HegdeDepartment of Life Sciences, Shiv Nadar Institution of Eminence, NH91, Tehsil Dadri, Greater Noida, Uttar Pradesh , 201314, India.
Abhik DuttaInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India.
Siddham JasoriaInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India.
Sunny KatariaInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India.
Ashutosh SinghDepartment of Life Sciences, Shiv Nadar Institution of Eminence, NH91, Tehsil Dadri, Greater Noida, Uttar Pradesh , 201314, India.
Colin JamoraInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India. colin.jamora@snu.edu.in.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKeratinocyte stem cells are essential for maintaining epidermal homeostasis and enabling efficient tissue repair. Regulation of their self-renewal and differentiation is critical, as its disruption can impair regeneration and drive pathological conditions such as chronic wounds and cancer. We previously identified the matricellular protein Mindin as a key regulator of keratinocyte stemness through its interaction with the αMβ2 (CD11b/CD18) integrin and subsequent activation of the transcription factor STAT3. However, the mechanism connecting Mindin and integrin at the cell surface to the intracellular activation of STAT3 remained undefined.

methodsWe employ biochemical and imaging analysis along with molecular dynamics simulations to dissect Mindin-integrin-STAT3 signalling in primary mouse keratinocytes. Stemness of epidermal keratinocytes are assessed using bulk RNA sequencing, quantitative PCR, and cell-based assays.

resultsOur work demonstrates that the F-Spondin domain of Mindin constitutes the minimal integrin-binding module required to initiate downstream signalling. F-Spondin binding to the integrin at the plasma membrane does not elicit the full activation state of the integrin. Instead, it promotes Src-kinase dependent endocytosis of the integrin receptor to the early endosomes. Analysis of integrin conformational dynamics reveals that the acidic environment of early endosomes is essential to achieve a signalling-competent state. This mechanism extends to pathological contexts, as we demonstrate a requirement for endocytosis in activating STAT3 signalling and preserving stem-like properties in a cancer stem cell model.

conclusionsThese findings highlight a previously unrecognized layer of spatial control in integrin signalling, confirming endosomal trafficking as a critical determinant of stem cell behaviour and offering new conceptual and therapeutic opportunities across regenerative biology and cancer.

Indexed as

EndocytosisExtracellular Matrix ProteinsKeratinocytesSTAT3 Transcription FactorStem CellsAnimalsEndosomesHumansMiceSignal TransductionExtracellular Matrix ProteinsSTAT3 Transcription FactorEndosomal acidificationF-SpondinKeratinocyte stemnessSTAT3 activationαMβ2 endocytosis

Identifiers

PMID42237193
PMCPMC13501600

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