Transmembrane-4 L-six family member-1 (TM4SF1) is a member of the L6 family and functions as a signal transducer to regulate tumor cell behaviors. However, the function and mechanism of TM4SF1 in esophageal squamous cell carcinoma (ESCC) metastasis remains unclear. Here, we find that TM4SF1 expression is increased and positively correlated with clinical TNM stage, N classification, differentiation, tumor size, and poor prognosis in ESCC patients. Interestingly, we demonstrate that TM4SF1 promotes ESCC cell adhesion, spreading, migration, and invasion, but not cell proliferation, in a laminin-dependent manner by interacting with integrin α6. Mechanistically, the TM4SF1/integrin α6/FAK axis signal pathway mediates cell migration under laminin-coating condition. Inhibiting FAK or knocking down TM4SF1 can attenuate TM4SF1-mediated cell migration and lung metastasis. Clinically, the TM4SF1/integrin α6/FAK axis positively correlates with ESCC. Altogether, these findings reveal a new mechanism of TM4SF1 in promoting ESCC metastasis via binding to integrin α6 and suggest that the cross-talk between TM4SF1 and integrin α6 may serve as a therapeutic target for ESCC.

BackgroundEmotion and quality of life may have been impacted by the coronavirus disease 2019 (COVID-19) crisis, especially in the lockdown. The impact of temporomandibular disorders (TMD) symptoms and tooth loss on mental status and Oral Health-Related Quality of Life (OHRQoL) are not fully understood in a stressful situation.ObjectivesWe aimed to investigate whether TMD and tooth loss were the impaired risks of psychological states and OHRQoL in COVID-19 lockdown, and attempt to explore other potential risk factors.MethodsThis cross-sectional study surveyed residents via an online self-reported questionnaire, when Yangzhou was in lockdown. Demographic data, clinical information, the level of anxiety, depression and OHRQoL were collected and analyzed.ResultsPainful TMD symptoms and tooth loss are the risks of more severe anxiety and depression. TMD symptoms and tooth loss worsened OHRQoL. Lower education degree (OR: 6.31, P = 0.019), TMD-related pain symptoms (OR: 10.62, P = 0.005), tooth loss (OR: 3.12, P = 0.035), sleep disorders (OR: 2.92, P = 0.049) and relatively close contacts (OR: 3.95, P = 0.020) were verified as risk factors for increased level of anxiety. With respect to depression, low socio-economic status (OR: 6.22, P = 0.021), TMD-related pain (OR: 7.35, P = 0.012), tooth loss (OR: 4.48, P = 0.009), sleep disorders (OR: 5.13, P = 0.007) and relatively close contacts (OR: 12.94, P = 0.001) were identified as independent factors for developing depression. Additionally, drinking (B: −2.584, P = 0.013) and never going to the dental clinic (B: −3.675, P = 0.024) were relevant to better OHRQoL, while TMD without pain (B: 2.797, P = 0.008), TMD-related pain (B: 12.079, P < 0.001), tooth loss (B: 2.546, P = 0.006), sleep disorders (B: 2.598, P = 0.003) were independent factors for impaired OHRQoL.ConclusionPainful TMD symptoms, tooth loss and sleep disorders were the impaired risks of psychological states. TMD symptoms and tooth loss damaged OHRQoL when the city was in lockdown. Therefore, individualized psychological counseling is supposed to maintain control of mental health and OHRQoL under the stressful event.