Epidemiological and clinical studies over the past two decades have provided strong evidence that genetic elements interacting with environmental components can individually and collectively influence one’s susceptibility to cancer. In addition to tumorigenic properties, numerous environmental factors, such as nutrition, chemical carcinogens, and tobacco/alcohol consumption, possess pro-invasive and pro-metastatic cancer features. In contrast to traditional cancer treatment, modern therapeutics not only take into account an individual’s genetic makeup but also consider gene–environment interactions. The current review sharpens the focus by elaborating on the impact that environmental factors have on the pathogenesis and progression of head and neck cancer and the underlying molecular mechanisms involved. Recent advances, challenges, and future perspectives in this area of research are also discussed. Inhibiting key environmental drivers of tumor progression should yield survival benefits for patients at any stage of head and neck cancer.

Spanning from the mitochondria’s outer surface to the inner membrane, the nuclear-encoded protein ATAD3A maintains vital roles in regulating mitochondrial dynamics, homeostasis, metabolism, and interactions with the endoplasmic reticulum. Recently, elevated levels of ATAD3A have been reported in several types of cancer and to be tightly correlated with cancer development and progression, including increased cancer cell potential of proliferation, metastasis, and resistance to chemotherapy and radiotherapy. In the current review, we reveal ATAD3A as the link between mitochondrial functions and cancer biology and the accumulating evidence presenting ATAD3A as an attractive target for the development of novel cancer therapy to inhibit aberrant cancer metabolism and progression.

Background: Ufm1-specific ligase 1 (Ufl1) and Ufm1-binding protein 1 (Ufbp1), as putative targets of ubiquitin-fold modifier 1 (Ufm1), have been implicated in several pathogenesis-related signaling pathways. However, little is known about their functional roles in liver disease. Methods: Hepatocyte-specific Ufl1^Δ/Δhep and Ufbp1^Δ/Δhep mice were used to study their role in liver injury. Fatty liver disease and liver cancer were induced by high-fat diet (HFD) and diethylnitrosamine (DEN) administration, respectively. iTRAQ analysis was employed to screen for downstream targets affected by Ufbp1 deletion. Co-immunoprecipitation was used to determine the interactions between the Ufl1/Ufbp1 complex and the mTOR/GβL complex. Results: Ufl1^Δ/Δhep or Ufbp1^Δ/Δhep mice exhibited hepatocyte apoptosis and mild steatosis at 2 months of age and hepatocellular ballooning, extensive fibrosis, and steatohepatitis at 6–8 months of age. More than 50% of Ufl1^Δ/Δhep and Ufbp1^Δ/Δhep mice developed spontaneous hepatocellular carcinoma (HCC) by 14 months of age. Moreover, Ufl1^Δ/Δhep and Ufbp1^Δ/Δhep mice were more susceptible to HFD-induced fatty liver and DEN-induced HCC. Mechanistically, the Ufl1/Ufbp1 complex directly interacts with the mTOR/GβL complex and attenuates mTORC1 activity. Ablation of Ufl1 or Ufbp1 in hepatocytes dissociates them from the mTOR/GβL complex and activates oncogenic mTOR signaling to drive HCC development. Conclusions: These findings reveal the potential role of Ufl1 and Ufbp1 as gatekeepers to prevent liver fibrosis and subsequent steatohepatitis and HCC development by inhibiting the mTOR pathway.

Increasing evidence indicates that cancer metastasis is regulated by specific genetic pathways independent of those controlling tumorigenesis and cancer growth. WASF3, a Wiskott–Aldrich syndrome protein family member, appears to play a major role not only in the regulation of actin cytoskeleton dynamics but also in cancer cell invasion/metastasis. Recent studies have highlighted that WASF3 is a master regulator and acts as a pivotal scaffolding protein, bringing the various components of metastatic signaling complexes together both spatially and temporally. Herein, targeting WASF3 at the levels of transcription, protein stability, and phosphorylation holds great promise for metastasis suppression, regardless of the diverse genetic backgrounds associated with tumor development. This review focuses on the critical and distinct contributions of WASF3 in the regulation of signal pathways promoting cancer cell invasion and metastasis.

To synthesise and evaluate a bioactive poly(amidoamine)-inositol hexakisphosphate (PAMAM-IP6) conjugate as a selective extrafibrillar dentine demineralisation conditioner designed to preserve intrafibrillar minerals, inhibit dentinal protease activity, and enhance the durability of resin-dentine bonds. The conjugate was synthesised by conjugating IP6 to high-molecular weight PAMAM dendrimer with amino terminal groups and characterised using ATR-FTIR, proton NMR, and ¹³C NMR spectroscopy. Calcium chelation capacity was determined by inductively coupled plasma-atomic emission spectrometry. The optimal concentration and conditioning time were identified through tensile bond strength testing under wet- and dry-bonding conditions before and after thermocycling. Morphological features were evaluated using field emission scanning electron microscopy and atomic force microscopy. Endogenous gelatinolytic activity was evluated by in-situ zymography. Antibacterial efficacy against Streptococcus mutans and Enterococcus faecalis was analysed using live/dead bacterial staining. PAMAM-IP6 provided effective calcium chelation with partial extrafibrillar demineralisation and preservation of intrafibrillar minerals. Conditioning dentine with 50 mg/mL PAMAM-IP6 for 30 s achieved bond strengths comparable to those obtained with 37 % phosphoric acid and maintained stability after thermocycling. In-situ zymography revealed markedly reduced gelatinolytic activity relative to phosphoric acid. Antibacterial testing demonstrated substantial bacterial inhibition. PAMAM-IP6 showed low cytotoxicity towards human dental pulp cells. PAMAM-IP6 selectively demineralises extrafibrillar dentine, preserves collagen integrity, inhibits endogenous proteases, and exhibits antibacterial activity, thereby improving the durability of resin-dentine bonds. The PAMAM-IP6 conditioner offers a biomodulatory approach for dentine bonding by preserving intrafibrillar minerals and preventing collagen degradation. Its protease-inhibiting and antibacterial properties support improved clinical longevity of adhesive restorations and enable reliable bonding under both wet and dry bonding conditions.