HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling

Abstract

Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor. Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy. However, the molecular details of Tid1-mediated anti-metastasis remain elusive.Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins. Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis. The roles of Tid1-interacting client proteins in metastasis were validated both in vitro and in vivo. The interacting partner and downstream target of Tid1-interacting client protein were determined.Results: Herein, we first revealed that Galectin-7 was one of the Tid1-interacting client proteins. An inverse association of protein expression profile between Tid1 and Galectin-7 was determined in HNSCC patients. Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC. Furthermore, Tid1 abolished the nuclear translocation of Galectin-7 and suppressed Galectin-7-induced tumorigenesis and metastasis. Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate. Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7. Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.

Cancer Cell Membrane‐Coated Nanoparticles for Personalized Therapy in Patient‐Derived Xenograft Models

“…Herein, by using PDX models, we tested the feasibility of the cell membrane‐coated nanoplatform in a preclinical cancer treatment scenario. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide and affects 600 000 new patients each year . In this work, we first collected tumor tissues from three patients bearing different regions of HNSCC to develop PDX cell/mouse models ( Scheme ).…”

Ganoderma microsporum immunomodulatory protein, GMI, promotes C2C12 myoblast differentiation in vitro via upregulation of Tid1 and STAT3 acetylation

“…Conversely, Tid1 gene knockdown enhances cancer cell malignancy such as cell migration and invasion in vitro, and tumorigenicity in vivo [15]. Additionally, Tid1 abrogates the Galectin-7/TCF3/MMP9 axis to repress the cancer metastasis [16]. We also report the participation of Tid1 in early embryogenesis [20], T cells development [21], muscular development and mitochondrial biogenesis [22] in normal development.…”

“…Tid1 has been identified as a tumor suppressor [15][16][17][18][19]. Previously, we have demonstrated that cell proliferation is inhibited in Tid1 overexpressed head and neck squamous cell carcinoma (HNSCC) cells.…”

Loss of Tid1/DNAJA3 Co-Chaperone Promotes Progression and Recurrence of Hepatocellular Carcinoma after Surgical Resection: A Novel Model to Stratify Risk of Recurrence

“…Tid1, acting as a tumor suppressor, interacts with EGFR/HSP70/HSP90 by DnaJ domain and causes EGFR degradation in non-small cell lung cancer (NSCLC) [ 18 ] and in head and neck squamous cell carcinoma (HNSCC). Overexpression of Tid1 in HNSCC cell lines enables the inhibition of in vitro malignancy and in vivo xenotransplantation tumorigenicity and metastasis [ 19 ]. Additionally, we reported that the HNSCC patients with higher expression of Tid1 have better overall survival [ 19 , 20 ].…”

“…Overexpression of Tid1 in HNSCC cell lines enables the inhibition of in vitro malignancy and in vivo xenotransplantation tumorigenicity and metastasis [ 19 ]. Additionally, we reported that the HNSCC patients with higher expression of Tid1 have better overall survival [ 19 , 20 ]. Most recently, we also discovered that Tid1 can function as a tumor suppressor in gastric cancer progression [ 21 ].…”