Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is overexpressed and activated in many cancer types. FAK regulates diverse cellular processes, including growth factor signaling, cell cycle progression, cell survival, cell motility, angiogenesis, and the establishment of immunosuppressive tumor microenvironments through kinase-dependent and kinase-independent scaffolding functions in the cytoplasm and nucleus. Mounting evidence has indicated that targeting FAK, either alone or in combination with other agents, may represent a promising therapeutic strategy for various cancers. In this review, we summarize the mechanisms underlying FAK-mediated signaling networks during tumor development. We also summarize the recent progress of FAK-targeted small-molecule compounds for anticancer activity from preclinical and clinical evidence.

Cancer metabolic reprogramming promotes tumorigenesis and metastasis; however, the underlying molecular mechanisms are still being uncovered. In this study, we show that the glycolytic enzyme aldolase A (ALDOA) is a key enzyme involved in lung cancer metabolic reprogramming and metastasis. Overexpression of ALDOA increased migration and invasion of lung cancer cell lines in vitro and formation of metastatic lung cancer foci in vivo. ALDOA promoted metastasis independent of its enzymatic activity. Immunoprecipitation and proteomic analyses revealed γ-actin binds to ALDOA; blocking this interaction using specific peptides decreased metastasis both in vitro and in vivo. Screening of clinically available drugs based on the crystal structure of ALDOA identified raltegravir, an antiretroviral agent that targets HIV integrase, as a pharmacologic inhibitor of ALDOA-γ-actin binding that produced antimetastatic and survival benefits in a xenograft model with no significant toxicity. In summary, ALDOA promotes lung cancer metastasis by interacting with γ-actin. Targeting this interaction provides a new therapeutic strategy to treat lung cancer metastasis.Significance: This study demonstrates the role of aldolase A and its interaction with γ-actin in the metastasis of non–small lung cancer and that blocking this interaction could be an effective cancer treatment.

Influenza B virus infection is generally considered to be mild and is rarely associated pulmonary cardiovascular involvement in adults. However fatal complications may occur. A 43-year-old previously healthy Taiwanese male came to our emergency department due to high fever, chills, general malaise and myalgia for about 4 days. An influenza rapid test from a throat swab was negative. Chest radiography showed mild left lung infiltration and levofloxacin was prescribed. However, progressive shortness of breath and respiratory failure developed 48 h later after hospitalization. Emergent intubation was performed and he was transferred to the intensive care unit where oseltamivir (Tamiflu, Roche) 75 mg orally twice daily was given immediately. In the intensive care unit, cardiac catheterization revealed normal coronary arteries. However, a markedly elevated cardiac enzyme level (Troponin I level was up to 71.01 ng/ml), a positive cardiac magnetic resonance imaging findings and no coronary artery stenosis led to the diagnosis of acute myocarditis. Subsequent real-time polymerase chain reaction of endotracheal aspirates was positive for influenza B. His condition gradually improved and he was successfully weaned from the ventilator on day 22. He was discharged without prominent complications on day 35. Influenza B infection is not always a mild disease. Early detection, early administration of antiviral agents, appropriate antibiotics and best supportive care, is still the gold standard for patients such as the one reported.

Follistatin-like protein 1 (FSTL1) plays a critical role in lung organogenesis, but is downregulated during lung cancer development and progression. The prognostic significance and functional consequences of FSTL1 downregulation in lung cancer are unclear. Here, reduced levels of FSTL1 were detected in various tumors compared with normal tissues and were associated with poor clinical outcome in patients with non–small cell lung cancer, particularly those with lung adenocarcinoma. FSTL1 expression negatively correlated with the metastatic potential of lung cancer cells. Antibody-based neutralization of extracellular FSTL1 increased cellular migration/invasion while addition of recombinant FSTL1 protein diminished the metastatic capacity of lung cancer cells in vitro and in vivo. Notably, treatment with FSTL1 effectively prevented the metastatic progression of lung cancer cells in an orthotopic animal model. Mechanistically, FSTL1 directly bound to the proform of secreted phosphoprotein 1 (SPP1)/osteopontin, restraining proteolytic activation of SPP1, which led to inactivation of integrin/CD44-associated signaling and rearrangement of the actin cytoskeleton. Combined low expression of FSTL1 and high expression of SPP1 predicted a poorer prognosis for patients with lung cancer. This study highlights the novel interaction between FSTL1 and SPP1 and new opportunities to effectively target SPP1-driven metastatic cancers characterized by FSTL1 downregulation. Significance: These findings describe the novel interaction between FSTL1 and SPP1 and its role in the metastatic progression of lung adenocarcinoma.