Biology subjects

Andl, T.

Publications and source records attributed to Andl, T..

4 recordsLinked to original sources

bioRxiv2026

BMP6 coordinates dermal papilla and epithelial cell states for hair follicle engineering and regeneration

Human hair follicle engineering is hindered by the rapid loss of inductive competence in culture-expanded dermal papilla (DP) fibroblasts. Here we show that bone morphogenetic protein 6 (BMP6) maintains and restores DP-associated characteristics while promoting follicular epithelial differentiation by restricting keratinocyte (KC) proliferation and inducing hair follicle-associated marker expression. Human follicle transcriptomics further linked BMP activity to DP identity and follicular epithelial differentiation. Genetic mouse studies demonstrate that BMP6 in Sox2-positive DP cells contributes to normal anagen onset, progression, and maintenance. Gain- and loss-of-function studies in KC-DP organoids show that BMP6 promotes epithelial-mesenchymal organization and spatially patterned follicular structures. In vivo, topical BMP6 promotes anagen onset, whereas BMP6 overexpression restores the hair follicle-generating capacity of late-passage human DP fibroblasts. Together, these findings identify BMP6 as a compartment-dependent regulator that enhances human DP competence and promotes epithelial differentiation, supporting regenerative hair follicle formation and engineering with culture-expanded DP cells.

developmental biology↗

bioRxiv2025

Actin-modulated nuclear shape controls adaptive reprogramming in cancer-associated fibroblasts

Cancer-associated fibroblasts (CAFs) exhibit striking plasticity, enabling them to adapt to external cues such as therapeutic and mechanical stress in the tumor microenvironment (TME). Here, we uncover a shared mechanotransduction pathway through which both BRAF inhibition and matrix stiffness converge in nuclear remodeling to drive CAF activation. Mechanistically, BRAF inhibitors (BRAFis) accelerate RAS-dependent RAF homo and heterodimerization and ERK signaling, leading to GSK-3{beta} inactivation and Rho kinase (ROCK) activation. In parallel, stiff substrates engage integrin receptors to directly activate ROCK signaling. Activation of ROCK induces actin stress fiber assembly, generating mechanical forces that deform the nucleus. In both contexts, nuclear reshaping promotes {beta}-catenin translocation and actin polymerization through a feedback loop that continuously enforces CAF activation and promotes melanoma progression. Notably, pharmacological inhibition of ROCK activity blocks both BRAFi- and stiffness-induced nuclear remodeling and {beta}-catenin accumulation, identifying the ROCK-cytoskeleton-nucleus axis as a critical regulator of CAF adaptation and functionality. Collectively, these findings reveal a mechanically tuned nuclear signaling hub that integrates chemical and physical cues to promote stromal adaptation and suggest ROCK inhibition as a strategy to counteract therapy-induced fibroblast reprogramming and improve therapy response.

cancer biology↗

bioRxiv2021

BRAF inhibitors reprogram cancer-associated fibroblasts to drive matrix remodeling and therapeutic escape in melanoma

The tumor stroma and its cellular components are known to play an important role in tumor resilience towards treatment. Here, we report a novel resistance mechanism in melanoma that is elicited by BRAF inhibitors (BRAFi)-induced non-canonical nuclear {beta}-catenin signaling in cancer-associated fibroblasts (CAFs). Our study reveals that BRAFi leads to an expanded CAF population with increased {beta}-catenin nuclear accumulation and enhances their biological properties. This CAF subpopulation is essential for melanoma cells to grow and resist to BRAFi/MEK inhibitors (MEKi). Mechanistically, BRAFi induces BRAF and CRAF dimerization and subsequently the activation of ERK signaling in CAFs, leading to the inactivation of the {beta}-catenin destruction complex. By RNA-Seq, periostin (POSTN) is identified as a major downstream effector of {beta} catenin in CAFs and can compensate for the loss of {beta}-catenin in CAFs in conferring melanoma cell BRAFi/MEKi resistance. Moreover, POSTN reactivates the ERK pathway, which is inhibited by BRAFi/MEKi, in melanoma cells through PI3K/AKT signaling. Our data underscore the roles of BRAFi-induced CAF reprogramming in matrix remodeling and therapeutic escape of melanoma cells and reveal POSTN as an important matrix target to eliminate BRAFi/MEKi resistance in melanoma.

cancer biology↗

bioRxiv2020

LncRNA PAINT is Associated with Aggressive Prostate Cancer and Dysregulation of Slug and Related Genes

Long non-coding RNAs (lncRNAs) play regulatory roles in cellular processes and their aberrant expression may drive cancer progression. Here we report the function of a lncRNA PAINT (Prostate Cancer Associated Intergenic Non-Coding Transcript) in promoting prostate cancer (PCa) progression. Upregulation of PAINT was noted in advanced stage and metastatic PCa. Inhibition of PAINT decreased cell proliferation, S-phase progression, increased expression of apoptotic markers, and improved sensitivity to docetaxel and Aurora kinase inhibitor VX-680. Inhibition of PAINT decreased cell migration and reduced expression of Slug and Vimentin. Ectopic expression of PAINT suppressed E-cadherin, increased S-phase progression and cell migration. PAINT expression in PCa cells induced larger colony formation and higher expression of mesenchymal markers. Transcriptome analysis followed by qRT-PCR validation showed differentially expressed genes involved in epithelial mesenchymal transition (EMT), apoptosis and drug resistance in PAINT-expressing cells. Our study establishes an oncogenic function of PAINT in PCa.

cancer biology↗