Endosomal protein expression of γ1-adaptin is associated with tumor growth activity and relapse-free survival in breast cancer

Sep 22, 2026

Upload by Anda

Study explores how γ1-adaptin, a subunit of adaptor protein complex-1 (AP-1), relates to breast cancer progression and relapse-free survival. Background links AP-1 subunit expression to proliferation and malignancy, prompting analysis of immunohistochemical γ1-adaptin in patient tissues. SK-BR-3 cells with γ1-adaptin depletion were used for functional assays, while localization was assessed by immunohistochemistry and double immunohistofluorescence. Results show γ1-adaptin depletion suppresses growth, migration, and invasion, and high γ1-adaptin intensity correlates with worse relapse-free survival and acts as an independent prognostic factor.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Background

Materials and methods

Results

Conclusion

Keywords

Introduction

Breast Cancer (2024) 31:305–316 [https://doi.org/10.1007/s12282-023-01539-1](https://doi.org/10.1007/s12282-023-01539-1) Endosomal protein expression of γ1‑adaptin is associated with tumor growth activity and relapse‑free survival in breast cancer Nobuhiro Hoshi1 · Takefumi Uemura2 · Kazunoshin Tachibana1 · Sadahiko Abe1 · Yuko Murakami‑Nishimagi1 · Maiko Okano1 · Masaru Noda1 · Katsuharu Saito3 · Koji Kono3 · Tohru Ohtake1 · Satoshi Waguri2 Received: 20 October 2022 / Accepted: 20 December 2023 / Published online: 24 January 2024 © The Author(s) 2024 Abstract Background γ1-Adaptin is a subunit of adaptor protein complex-1 (AP-1), which regulates intracellular transport between the trans-Golgi network (TGN) and endosomes. Since expression levels of AP-1 subunits have been reported to be associated with cell proliferation and cancer malignancy, we investigated the relationships between the immunohistochemical expression of γ1-adaptin and both clinicopathological factors and relapse-free survival (RFS) in breast cancer tissue. Materials and methods SK-BR-3 cell line depleted of γ1-adaptin was used for cell proliferation, migration, and invasion assay. Intracellular localization of γ1-adaptin was examined with immunohistochemistry (IHC) using an antibody against γ1-adaptin, and with double immunohistofluorescence (IHF) microscopy using markers for the TGN and endosome.γ1-Adaptin intensities in IHC samples from 199 primary breast cancer patients were quantified and assessed in relation to clinicopathological factors and RFS. Results Cell growth, migration, and invasion of SK-BR-3 cells were significantly suppressed by the depletion of γ1-adaptin. Although the staining patterns in the cancer tissues varied among cases by IHC, double IHF demonstrated that γ1-adaptin was mainly localized in EEA1-positive endosomes, but not in the TGN. γ1-Adaptin intensity was significantly higher in the tumor regions than in non-tumor regions. It was also higher in patients with Ki-67 (high), ER (–), PgR (–), and HER2 (+) . Among subtypes of breast cancer, γ1-adaptin intensity was higher in HER2 than in luminal A or luminal B. The results of the survival analysis indicated that high γ1-adaptin intensity was significantly associated with worse RFS, and this association was also observed in group with ER (+), PgR (+), HER2 (–), Ki-67 (high), or luminal B. In addition, the Cox proportional hazards model showed that high γ1-adaptin intensity was an independent prognostic factor. Conclusion These results suggest that the endosomal expression of γ1-adaptin is positively correlated with breast cancer malignancy and could be a novel prognostic marker. Keywords γ1-Adaptin · Clathrin adaptor · Adaptor protein complex-1 · AP-1 · Endosome Introduction Breast cancer is the leading cause of cancer death among females worldwide, according to GLOBOCAN 2020 estimates [1] . It is a complex disease, and currently classified * Satoshi Waguri [waguri@fmu.ac.jp](waguri@fmu.ac.jp) 1 Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan 2 Department of Anatomy and Histology, Fukushima Medical University School of Medicine, Fukushima, Japan 3 Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan into four subtypes: luminal A, luminal B, human epidermal growth factor receptor type 2 (HER2)-positive, and triple-negative breast cancer (TNBC). They reflect intrinsic biological subtypes [2] determined by the immunohistochemistry (IHC) of estrogen receptor (ER), progesterone receptor (PgR), HER2, and a cell proliferation marker Ki-67 [3, 4] . Importantly, these subtypes are strongly associated with treatment strategies and prognosis; e.g., TNBC shows poorer prognosis than the luminal types of breast cancer [5, 6]. However, late recurrence was higher in patients with ER-positive primary tumors [7] and pathological complete response following preopera

FAQs

What role does γ1-adaptin play in relation to AP-1 and endosomal transport?

γ1-adaptin is a γ1 subunit of AP-1 (adaptor protein complex-1), which regulates intracellular transport between the trans-Golgi network and endosomes.

How were the effects of γ1-adaptin depletion tested in this study?

SK-BR-3 cells depleted of γ1-adaptin were used for proliferation, migration, and invasion assays, assessing functional impact on cancer cell behavior.

What clinical outcome was associated with higher γ1-adaptin intensity?

High γ1-adaptin intensity was significantly associated with worse relapse-free survival, and Cox proportional hazards modeling showed it as an independent prognostic factor.

Sep 22, 2026

Upload by Anda