Mechanism underlying follicular hyperproliferation and oncogenesis in hidradenitis suppurativa

Lin Jin; Mahendra P Kashyap; Yunjia Chen; Jasim Khan; Yuanyuan Guo; Jari Q Chen; Madison B Lee; Zhiping Weng; Allen Oak; Prasanth Patcha; Tiffany Mayo; Rajesh Sinha; Venkatram Atigadda; Shahid M Mukhtar; Jessy S Deshane; Chander Raman; Carly Elston; Boni E Elewski; Craig A Elmets; Mohammad Athar

doi:10.1016/j.isci.2023.106896

Mechanism underlying follicular hyperproliferation and oncogenesis in hidradenitis suppurativa

iScience. 2023 May 19;26(6):106896. doi: 10.1016/j.isci.2023.106896. eCollection 2023 Jun 16.

Authors

Lin Jin^{1

2

3}, Mahendra P Kashyap^{2

3}, Yunjia Chen⁴, Jasim Khan^{2

3}, Yuanyuan Guo^{2

3}, Jari Q Chen⁵, Madison B Lee⁶, Zhiping Weng^{1

2

3}, Allen Oak², Prasanth Patcha⁷, Tiffany Mayo², Rajesh Sinha^{2

3}, Venkatram Atigadda², Shahid M Mukhtar⁸, Jessy S Deshane⁹, Chander Raman², Carly Elston¹⁰, Boni E Elewski², Craig A Elmets², Mohammad Athar^{1

2

3}

Affiliations

¹ Center for Epigenomics and Translational Research in Inflammatory Skin Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
² Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
³ UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁴ Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁵ Hoover High School, Hoover, Birmingham, AL 35244, USA.
⁶ School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁷ Division of Plastic Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁸ Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁹ Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
¹⁰ Department of Dermatology and Dermatopathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Abstract

Hidradenitis suppurativa (HS) is a skin disorder that causes chronic painful inflammation and hyperproliferation, often with the comorbidity of invasive keratoacanthoma (KA). Our research, employing high-resolution immunofluorescence and data science approaches together with confirmatory molecular analysis, has identified that the 5'-cap-dependent protein translation regulatory complex eIF4F is a key factor in the development of HS and is responsible for regulating follicular hyperproliferation. Specifically, eIF4F translational targets, Cyclin D1 and c-MYC, orchestrate the development of HS-associated KA. Although eIF4F and p-eIF4E are contiguous throughout HS lesions, Cyclin D1 and c-MYC have unique spatial localization and functions. The keratin-filled crater of KA is formed by nuclear c-MYC-induced differentiation of epithelial cells, whereas the co-localization of c-MYC and Cyclin D1 provides oncogenic transformation by activating RAS, PI3K, and ERK pathways. In sum, we have revealed a novel mechanism underlying HS pathogenesis of follicular hyperproliferation and the development of HS-associated invasive KA.

Keywords: Biochemistry; Biological sciences; Medical biochemistry.

Abstract

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