Here, we show that in a mouse model of polyomavirus middle T antigen-induced mammary tumorigenesis, loss of Kindlin-1 reduced early pulmonary arrest and later development of lung metastasis.
Using a chronic constriction injury (CCI) rat model of neuropathic pain, we investigated the expression levels of kindlin-1 during neuropathic pain and the influences of kindlin-1 on regulating pain sensitivity.
Animals in the CCI + kindling-1 shRNA and CCI + kindlin-1 groups were given kindlin-1 shRNA or kindlin-1 virus infection to reduce or overexpress kindlin-1, respectively.
Their biological significance in skin is underscored by two genetic disorders, the Kindler syndrome and the interstitial lung disease, nephrotic syndrome and epidermolysis bullosa, in which mutations affect focal adhesion proteins, kindlin-1 and the integrin α3 subunit, respectively.
Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both <i>P</i>=0.01) and disease-free (<i>P</i>=0.02 and 0.01, respectively) survivals of osteosarcoma patients.
In conclusion, aberrant expression of Kindlin-1 and Kindlin-2 may function as reliable markers for progression and prognosis in osteosarcoma patients, especially for tumor recurrence.
Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both <i>P</i>=0.01) and disease-free (<i>P</i>=0.02 and 0.01, respectively) survivals of osteosarcoma patients.
Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both <i>P</i>=0.01) and disease-free (<i>P</i>=0.02 and 0.01, respectively) survivals of osteosarcoma patients.
Despite the fact that loss-of-function mutations in the FERMT1 gene, encoding kindlin-1, have been shown to cause the syndrome in numerous patients, a small number of typical cases of KS in which FERMT1 mutations could not be identified has raised the possibility that the disorder may be genetically heterogeneous.
All patients presented duplication mutations (c.456dupA and c.676dupC) in FERMT1, and slipped mispairing in direct nucleotide repeats was identified as the reversion mechanism in all investigated revertant skin spots.
Kindlin-1 expression was consistently higher in tumors than in normal tissues in various cancer types metastasizing to the lungs, including colon and bladder cancer.
Kindlin-1 expression was consistently higher in tumors than in normal tissues in various cancer types metastasizing to the lungs, including colon and bladder cancer.
Kindlin-1 expression was associated with metastasis-free survival in both breast and lung adenocarcinoma (breast cancer: hazard ratio of lung metastasis = 2.55, 95% confidence intervals [CI] = 1.39 to 4.69, P = .001; lung cancer: hazard ratio of metastasis = 1.96, 95% CI = 1.25 to 3.07, P = .001).
These results suggest a role for kindlin-1 in breast cancer lung metastasis and lung tumorigenesis and advance our understanding of kindlin-1 as a regulator of TGFβ signaling, offering new avenues for therapeutic intervention against cancer progression.
Kindlin-1 expression was associated with metastasis-free survival in both breast and lung adenocarcinoma (breast cancer: hazard ratio of lung metastasis = 2.55, 95% confidence intervals [CI] = 1.39 to 4.69, P = .001; lung cancer: hazard ratio of metastasis = 1.96, 95% CI = 1.25 to 3.07, P = .001).
Kindlin-1 expression was associated with metastasis-free survival in both breast and lung adenocarcinoma (breast cancer: hazard ratio of lung metastasis = 2.55, 95% confidence intervals [CI] = 1.39 to 4.69, P = .001; lung cancer: hazard ratio of metastasis = 1.96, 95% CI = 1.25 to 3.07, P = .001).
Kindlin-1 expression was consistently higher in tumors than in normal tissues in various cancer types metastasizing to the lungs, including colon and bladder cancer.
Kindlin-1 expression was associated with metastasis-free survival in both breast and lung adenocarcinoma (breast cancer: hazard ratio of lung metastasis = 2.55, 95% confidence intervals [CI] = 1.39 to 4.69, P = .001; lung cancer: hazard ratio of metastasis = 1.96, 95% CI = 1.25 to 3.07, P = .001).
Finally, Kindlin-1 depletion in an orthotopic mouse model statistically significantly inhibited breast tumor growth (P < .001) and lung metastasis (P = .003).