Overall, the data suggest that this extract of M. verticillata seeds could be a good candidate for treating hair loss by modulating the Wnt/β-catenin pathway in DPCs.

The number of people suffering from hair loss is increasing, and hair loss occurs not only in older men but also in women and young people. Prostaglandin D2 (PGD2) is a well-known alopecia inducer. However, the mechanism by which PGD2 induces alopecia is poorly understood. In this study, we characterized CXXC5, a negative regulator of the Wnt/β-catenin pathway, as a mediator for hair loss by PGD2. The hair loss by PGD2 was restored by Cxxc5 knock-out or treatment of protein transduction domain–Dishevelled binding motif (PTD-DBM), a peptide activating the Wnt/β-catenin pathway via interference with the Dishevelled (Dvl) binding function of CXXC5. In addition, suppression of neogenic hair growth by PGD2 was also overcome by PTD-DBM treatment or Cxxc5 knock-out as shown by the wound-induced hair neogenesis (WIHN) model. Moreover, we found that CXXC5 also mediates DHT-induced hair loss via PGD2. DHT-induced hair loss was alleviated by inhibition of both GSK-3β and CXXC5 functions. Overall, CXXC5 mediates the hair loss by the DHT-PGD2 axis through suppression of Wnt/β-catenin signaling.

Hair follicle stem cells (HFSCs) utilize glycolytic metabolism during their activation and anagen induction. However, the role of pyruvate kinase M2 (PKM2), which catalyzes the final step of glycolysis, in hair regeneration has not been elucidated. In this study, we investigated the expression pattern and activity of PKM2 during the depilation-induced anagen progression in mice. We found that TEPP-46, a selective activator of PKM2, enhanced hair re-growth and proliferation of HFSCs. PKM2 expression was increased via up-regulation of Wnt/β-catenin signaling, which is involved in hair regeneration. Moreover, a combined treatment with KY19382, a small molecule that activates Wnt/β-catenin signaling, and TEPP-46 significantly enhanced hair re-growth and wound-induced hair follicle neogenesis (WIHN). These results indicate that simultaneous activation of the PKM2 and Wnt/β-catenin signaling could be a potential strategy for treating alopecia patients.

A patient-derived organoid (PDO) is an in vitro three-dimensional model which shows similar features in phenotypic and genetic aspects with primary tissue from patients. PDOs are useful for preclinical studies including drug sensitivity tests of tumors from individual patients as well as development of novel targeted agents. Collectively, PDOs are recently introduced as an emerging platform for personalized medicine. We obtained a total of 100 surgical specimens from 100 patients with breast cancer at the Yonsei Cancer Center, Severance Hospital, Seoul, Korea. One of the tissue specimens was acquired from a breast cancer patient-derived xenograft model. We dissociated the tissues and isolated breast cancer primary tumor cells from the samples, and then the cells were cultured in basement membrane-like matrix in 3D manner with growth medium with supplements. We defined successful establishment of PDOs as continuous growth after 3 passaging. Among all 100 cases, 32 cases failed to culture or passage, however, 41 cases were successfully cultured over 3 passages. In addition, the remaining 27 cases are still in progress of establishment. Success rate of PDO was 68% (68/100). Subtypes of primary tumors of the PDO were 33.8% (23/68) of luminal A, 26.5% (18/68) of luminal B, 26.5% (18/68) of triple-negative, 5.9% (4/68) of triple-positive and 7.4% (5/68) of HER2-enriched. Success rates of each subtype were 69.7% (23/33) of luminal A, 72.0% (18/25) of luminal B, 66.7% (18/27) of triple-negative, 66.7% (4/6) of triple-positive and 55.6% (5/9) of HER2-enriched. Pathologic evaluation using immunohistochemistry revealed that PDOs showed similar morphologic and immunohistochemical features with primary tumors. The selective sensitivity of PARP inhibitor, olaparib, was confirmed in PDOs harboring mutant BRCA1/2 compared with BRCA1/2 wild-type PDOs. Overall, PDOs can be used as a real-time platform for drug sensitivity and screening analyses, and a robust tool for preclinical studies in breast cancer. Citation Format: Won-Ji Ryu, Shinyoung Park, Jeong Dong Lee, Yumi Hwang, Seongyeon Jo, Kweon Tae Yong, Ja Seung Koo, Min Hwan Kim, Joo Hyuk Sohn, Hyung Seok Park. Establishment of patient-derived organoid of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 178.

Cutaneous wound healing is a complex and dynamic process with high energy demand. The activation of glycolysis is essential for restoring the structure and function of injured tissues in wounds. Pyruvate kinase M2 (PKM2) is an enzyme that plays a crucial role in the last step of glycolysis. PKM2-mediated glycolysis is known to play an important role in diseases related to regeneration and inflammation. However, the role of PKM2 in wound healing has not been fully elucidated. In this study, we found that PKM2 expression and pyruvate kinase (PK) activity were increased with the activation of Wnt/β-catenin signaling during wound healing in mice. TEPP-46, an allosteric activator of PKM2, enhanced HaCaT human keratinocyte migration and cutaneous wound healing with an increment of PK activity. Moreover, we confirmed the effect of co-treatment with TEPP-46 and KY19382, a Wnt/β-catenin signaling activator through the interference with the CXXC-type zinc finger protein 5 (CXXC5) Dishevelled interaction, on wound healing. The combination treatment significantly accelerated wound healing, which was confirmed by the expression level of PCNA, keratin 14, and α-SMA. Furthermore, co-treatment induced angiogenesis in the wound beds. Overall, activation of both glycolysis and Wnt/β-catenin signaling has the potential to be used as a therapeutic approach for wound healing.