WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

Sep 21, 2026

Uploaded by Jiven

WNT7A, a Wnt family member, is investigated for its role and molecular mechanism in head and neck squamous cell carcinoma (HNSCC). TCGA transcriptome sequencing shows elevated WNT7A expression in tumors versus adjacent normal tissues, confirmed by real-time RT-PCR and immunohistochemistry. Unlike the expected canonical Wnt-β-catenin activation, WNT7A overexpression instead promotes FZD7/JAK1/STAT3 signaling, increasing cell proliferation, self-renewal, and resistance to apoptosis. Patient-derived xenograft data reveal high WNT7A with phosphorylated STAT3 correlating with tumor progression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Background on HNSCC

Wnt signaling pathway and cancer relevance

WNT7A roles across tumor types

Ongoing debate on WNT7A mechanisms

International Journal of Oral Science [www.nature.com/ijos](www.nature.com/ijos) WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling Qingling Huang 1, Yi Xiao2, Ting Lan2, Youguang Lu2,3, Li Huang4 ✉ and Dali Zheng 2 ✉ | | Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and necksquamous cell carcinoma (HNSCC) . According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our ﬁndings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These ﬁndings underscore the signiﬁcance of WNT7A in HNSCC progression and propose the targeting of key molecules within the | | | --- | --- | --- | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC. | | | | | International Journal of Oral Science (2024)16:7 ; [https://doi.org/10.1038/s41368-024-00279-y](https://doi.org/10.1038/s41368-024-00279-y) | | | | | | INTRODUCTION Head and neck squamous cell carcinoma (HNSCC) are a type of cancer that originates from the squamous cells lining the mucosal surfaces of the head and neck region, with an increasing incidence rate in recent years. It is estimated that as many as 380 000 new cases of HNSCC worldwide in 2020, with a trend towards earlier age of onset, particularly in high-incidence areas such as Asia and Africa.1 HNSCC usually exhibits an invasive growth pattern, frequently leading to regional lymph node or hematogenous metastases. Despite recent advances in treatment technologies, the unclear etiology and pathogenesis of HNSCC often result in limited therapeutic options and suboptimal outcomes, particularly in cases with local or distant metastases.2 The Wnt signaling pathway is a conserved signal transduction pathway in multicellular eukaryotes that exerts a wide range of biological effects. It plays a crucial role in various biological processes, such as cell growth, differentiation, proliferation, polarization, embryonic development, and stem cell self-renewal, and is involved in regulating most biological phenomena of life.3,4 Current research has established the crucial involvement of the Wnt signaling pathway in the onset and progression of numerous cancers.5,6 Aberrant activation of the Wnt signaling pathway affects the progress of several types of cells, enabling tumor cells to sustain and promote their stem cell phenotype, proliferation, and invasiveness. Among the identiﬁed cancers, over ten highincidence malignancies result from abnormal activation of the Wnt signaling pathway, including colorectal cancer,7 lung cancer,8 breast cancer,9 and childhood acute lymphoblastic leukemia.10 Several studies have conﬁrmed that Wnt signaling pathway imbalance can facilitate oral cancer development,11 and its abnormal activation can directly inﬂuence the prognosis of patients with oral cancer.2 The Wnt signaling pathway is a complex network involving 19 WNT ligand proteins, 10 receptor proteins, and multiple common or accessory proteins. The activation of this pathway, whether through canonical or non-canonical signaling, is always initiated by WNT ligand proteins. We analyze

FAQs

How does WNT7A expression differ between HNSCC tumors and adjacent normal tissues?

TCGA transcriptome data indicate higher WNT7A expression in HNSCC tumors than in adjacent normal tissues, and this is validated using real-time RT-PCR and immunohistochemistry.

Does WNT7A overexpression activate the canonical Wnt-β-catenin pathway in HNSCC?

No. WNT7A overexpression does not activate the canonical Wnt-β-catenin pathway in HNSCC; it is associated with activation of the FZD7/JAK1/STAT3 signaling axis.

What is the proposed therapeutic implication of the WNT7A-associated pathway?

The findings suggest targeting key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for more precise treatment of HNSCC.

Sep 21, 2026

Uploaded by Jiven