Development of novel therapy for cutaneous squamous cell cancer targeting TCHHL1

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16051
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of Toyama
• Principal Investigator: Mizawa Megumi 富山大学, 学術研究部医学系, 講師 (80401834)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: TCHHL / 皮膚癌 / 細胞増殖能 / 細胞死 / 乾癬

Outline of Final Research Achievements

In this study, we examined the role of Trichohyalin-like 1 (TCHHL1) protein in normal human keratinocytes (NHKs) and squamous cell carcinoma (SCC). We first developed a construct, which can produce a recombinant GFP-TCHHL1 protein in mammalian cells. The GFP-TCHHL1 proteins were diffusely localized in the cytoplasm. The signals of TCHHL1 were not colocalized with any organelles; however, the signals were strongly observed around the nuclei of cultured growing keratinocytes. We next examined an association with the cell growth in HSC-1 cells (a human SCC line), because TCHHL1 was expressed in the growing cells of cutaneous SCC. In HSC-1 cells, the knockdown of TCHHL1 suppressed cell proliferation and induced apoptosis. These cells showed an inhibition of phosphorylation of ERK1/2, AKT and STAT3, and the significant upregulation of FOXO1, BCL2 and BCL2L11. Accordingly, TCHHL1 is associated with survival of cutaneous SCC.

Free Research Field

皮膚科

Academic Significance and Societal Importance of the Research Achievements

皮膚有棘細胞癌は皮膚悪性腫瘍の一つである。進行例では有効な化学療法も少なく予後不良な疾患である。本研究ではTCHHL1の表皮内局在を中心とした機能解析と皮膚有棘細胞癌の増殖・生存への関与を検討し、皮膚有棘細胞癌の新規治療の標的となりうるかを検証した。本研究は表皮の増殖・分化における新たな機構が解明されるという学術的意義を持つ。また、皮膚有棘細胞癌における機能的役割が解明されることにより、皮膚有棘細胞癌に対する新規治療の開発につながるという社会的意義をもつ。