Esophageal cancer(EC) is one of the most lethal malignancies in China, but the etiology and risk factors remain unclear.The integrin-interacting proteins Kindlin-1 and Kindlin-2 are focal adhesion molecules that activate transmembrane receptor integrins and regulate tumor cell growth, invasion, and metastasis. Here, we report that Kindlin-I and Kindlin-2 are differentially expressed among Chinese EC patients. For this, Kindlin-1 and Kindlin-2 expression was evaluated in 220 EC patients by immunohistochemistry(IHC) and found to be correlated with the EC progression, along with a variety of epidemiologic parameters,including smoking,family EC history,and EC invasion status. Moreover,data downloaded from the Oncomine database revealed that both Kindlin-1 and Kindlin-2 were upregulated in ECs compared with normal esophageal tissues; although Kindlin-1 was highly expressed in well-differentiated tumors, whereas Kindlin-2 was more prevalent in poorly differentiated tumors. Collectively, these data suggest that Kindlin-1 may inhibit, while Kindlin-2 may promote, EC progression. This study,for the first time, linked the expression of Kindlin-1 and Kindlin-2 with EC family genetic background and living habits, which may help further our understanding of the various causes of EC.
LGR6 is a member of the G protein-coupled receptor family that plays a tumor-suppressive role in colon cancer. However, the relationship between LGR6 expression in patients and clinicopathological factors remains unclear. This study aimed to clarify whether the expression level of LGR6 is correlated with colon adenocarcinoma progression. Immunohistochemistry was used to detect LGR6 expression in colon adenoma tissues (n = 21), colon adenocarcinoma tissues (n = 156), and adjacent normal tissues (n = 124). The expression levels of LGR6 in colon adenoma and adenocarcinoma were significantly higher than those in normal colon epithelial tissues (P < 0.001). Low LGR6 expression predicted a short overall survival in patients with colon adenocarcinoma (log-rank test, P = 0.016). Univariate and multivariate survival analyses showed that, in addition to N and M classification, LGR6 expression served as an independent prognostic factor. Thus, low expression of LGR6 can be used as an independent prognostic parameter in patients with colon adenocarcinoma.
Kindlin-2 functions in the maintenance of homeostasis and in human diseases.This study investigated the interrelationship between Kindlin-2 expression in tissues and the corresponding germ layers from which these tissues originated.Kindlin-2 expression was examined in normal adult human organs and human cancer tissues by immunohistochemical analyses.Analysis of Kindlin-2 mRNA levels in adult human organs in the Oncomine dataset revealed Kindlin-2 is highly expressed in mesoderm-derived organs.However,Kindlin-2 was negative or weakly expressed in endoderm/ectoderm-derived organs.Interestingly,the abnormal expression of Kindlin-2 was observed in a variety of human cancers.In agreement with its expression profile in humans,Kindlin-2 was also highly expressed in mesoderm-derived organs in mouse embryos with the exception of strong Kindlin-2 expression in ectoderm-derived spinal cord and ganglia,tissues that are highly mobile during embryonic development.Importantly,we demonstrated the expression level of Kindlin-2 in adult organs correlated with their embryonic dermal origins and deregulation of Kindlin-2 in tissues is associated with tumor progression.This finding will help us understand the dual role of Kindlin-2 in the regulation of tumor progression and embryonic development.
Kindlin-2, a member of the Kindlin family focal adhesion proteins, plays an important role in cardiac development. It is known that defects in the Z-disc proteins lead to hypertrophic cardiomyopathy(HCM) or dilated cardiomyopathy(DCM). Our previous investigation showed that Kindlin-2 is mainly localized at the Z-disc and depletion of Kindlin-2 disrupts the structure of the Z-Disc. Here, we reported that depletion of Kindlin-2 leads to the disordered myocardial fibers, fractured and vacuolar degeneration in myocardial fibers. Interestingly, depletion of Kindlin-2 in mice induced cardiac myocyte hypertrophy and increased the heart weight. Furthermore, decreased expression of Kindlin-2 led to cardiac dysfunction and also markedly impairs systolic function. Our data indicated that Kindlin-2 not only maintains the cardiac structure but also is required for cardiac function.
Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes.However,genes that specifically promote basal-like breast cancer development remain largely unknown.Here,we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors.C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients.In human TCGA database,C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3,two transcription factors that regulate mammary gland stem cell fate.Enhanced expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5;depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3.These findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3.Taken together,we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer.
