Elevated YAP and Its Downstream Targets CCN1 and CCN2 in Basal Cell Carcinoma: Impact on Keratinocyte Proliferation and Stromal Cell Activation

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2014 Feb 4

PMID 24485923

Citations 42

Authors

Taihao Quan

Yiru Xu

Zhaoping Qin

Patrick Robichaud

Stephanie Betcher

Ken Calderone

Tianyuan He

Timothy M Johnson

John J Voorhees

Gary J Fisher

Affiliations

Soon will be listed here.

Abstract

Yes-associated protein (YAP) is a transcriptional co-activator of hippo signaling pathway, which plays an important role in organ size control and tumorigenesis. Here we report that YAP and its downstream transcriptional targets CCN1 and CCN2 are markedly elevated in keratinocytes in human skin basal cell carcinoma tumor islands. In human keratinocytes, knockdown of YAP significantly reduced expression of CCN1 and CCN2, and repressed proliferation and survival. This inhibition of proliferation and survival was rescued by restoration of CCN1 expression, but not by CCN2 expression. In basal cell carcinoma stroma, CCN2-regulated genes type I collagen, fibronectin, and α-smooth muscle actin were highly expressed. Furthermore, atomic force microscopy revealed increased tissue stiffness in basal cell carcinoma stroma compared to normal dermis. These data provide evidence that up-regulation of YAP in basal cell carcinoma impacts both aberrant keratinocyte proliferation, via CCN1, and tumor stroma cell activation and stroma remodeling, via CCN2. Targeting YAP and/or CCN1 and CCN2 may provide clinical benefit in basal cell carcinoma.

Citing Articles

CCN2 functions as a modulator of cell cycle regulation in human dermal fibroblasts.

Quan T, Shao Y, Purohit T, Jiang Y, Qin Z, Fisher G J Cell Commun Signal. 2025; 19(1):e70003.

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YAP/TAZ Signalling Controls Epidermal Keratinocyte Fate.

Pankratova M, Riabinin A, Butova E, Selivanovskiy A, Morgun E, Ulianov S Int J Mol Sci. 2024; 25(23).

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Tumor Cell Spatial Organization Directs EGFR/RAS/RAF Pathway Primary Therapy Resistance through YAP Signaling.

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CircHIPK2 Contributes Cell Growth in Intestinal Epithelial of Colitis and Colorectal Cancer through Promoting TAZ Translation.

Zeng X, Tang J, Zhang Q, Wang C, Qi J, Wei Y Adv Sci (Weinh). 2024; 11(34):e2401588.

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