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TMEM16A overexpression contributes to tumor invasion and poor prognosis of human gastric cancer through TGF-β signaling.

Liu F, Cao QH, Lu DJ, Luo B, Lu XF, Luo RC, Wang XG - Oncotarget (2015)

Bottom Line: A negative correlation between TMEM16A and E-cadherin was found in 367 GC specimens.TMEM16A silencing significantly decreased calcium activated chloride currents, impaired TGF-β secretion, reduced E-cadherin expression, and inhibited the migration and invasion without affecting proliferation of GC cells (AGS and BGC-823).Supplement of TGF-β reverted the effects of TMEM16A silencing on E-cadherin expression, cell migration and invasion.In conclusion, TMEM16A promotes invasion and metastasis in GC, and might be a novel prognostic biomarker and potential therapeutic target in the treatment of GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

ABSTRACT
TMEM16A is a newly identified calcium activated chloride channel, and has been reported to be overexpressed by various solid malignant cancers to promote proliferation and invasion, yet little is known about its role in gastric cancer(GC). Therefore, we investigated the role of TMEM16A in GC and its clinical significance by a retrospective analysis of 367 GC patients, and in vitro study was performed for validation and underlying molecular mechanism.TMEM16A was significantly upregulated and amplified in GC tissues, and its overexpression was positively correlated with disease stage, negatively with patient survival and identified as an independent prognostic factor for patient outcome. A negative correlation between TMEM16A and E-cadherin was found in 367 GC specimens. TMEM16A silencing significantly decreased calcium activated chloride currents, impaired TGF-β secretion, reduced E-cadherin expression, and inhibited the migration and invasion without affecting proliferation of GC cells (AGS and BGC-823). Supplement of TGF-β reverted the effects of TMEM16A silencing on E-cadherin expression, cell migration and invasion.In conclusion, TMEM16A promotes invasion and metastasis in GC, and might be a novel prognostic biomarker and potential therapeutic target in the treatment of GC.

No MeSH data available.


Related in: MedlinePlus

The expression of TMEM16A protein in gastric cancer, adjacent and normal tissuesA. A representative hematoxylin and eosin (HE) stained mounted section containing gastric cancer, adjacent and normal gastric mucosa (the upper row, original magnification, ×4) with enlarged view(the middle row, original magnification, ×40). The lower row displayed that TMEM16A was strongly expressed in gastric cancer(the right panel), whereas was moderately or weakly expressed in adjacent(the middle panel) and normal tissues(the left panel) (original magnification, ×40). B. Western blot analysis of TMEM16A protein expression in four pairs of matched gastric tumor (T) and adjacent non-tumor mucosa (N). Equal loading of protein was determined by β-actin.
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Figure 1: The expression of TMEM16A protein in gastric cancer, adjacent and normal tissuesA. A representative hematoxylin and eosin (HE) stained mounted section containing gastric cancer, adjacent and normal gastric mucosa (the upper row, original magnification, ×4) with enlarged view(the middle row, original magnification, ×40). The lower row displayed that TMEM16A was strongly expressed in gastric cancer(the right panel), whereas was moderately or weakly expressed in adjacent(the middle panel) and normal tissues(the left panel) (original magnification, ×40). B. Western blot analysis of TMEM16A protein expression in four pairs of matched gastric tumor (T) and adjacent non-tumor mucosa (N). Equal loading of protein was determined by β-actin.

Mentions: To confirm whether TMEM16A was overexpressed in GC, we performed immunohistochemistry (IHC) of mounted sections, western blotting of surgical samples. Expression of TMEM16A was found to be significantly higher in tumor tissues than that in adjacent non-tumor tissues (Fig. 1A, B). Then, TMEM16A protein expression in 367 GC tissues, corresponding lymph node metastatic lesions and normal gastric tissues was assessed by immunohistochemical staining. Consistent with above result, TMEM16A was strong expressed in GC and lymph node metastasis lesions on tissue microarray (TMA), whereas weak expressed in adjacent non-tumor gastric mucosal tissues.


TMEM16A overexpression contributes to tumor invasion and poor prognosis of human gastric cancer through TGF-β signaling.

Liu F, Cao QH, Lu DJ, Luo B, Lu XF, Luo RC, Wang XG - Oncotarget (2015)

The expression of TMEM16A protein in gastric cancer, adjacent and normal tissuesA. A representative hematoxylin and eosin (HE) stained mounted section containing gastric cancer, adjacent and normal gastric mucosa (the upper row, original magnification, ×4) with enlarged view(the middle row, original magnification, ×40). The lower row displayed that TMEM16A was strongly expressed in gastric cancer(the right panel), whereas was moderately or weakly expressed in adjacent(the middle panel) and normal tissues(the left panel) (original magnification, ×40). B. Western blot analysis of TMEM16A protein expression in four pairs of matched gastric tumor (T) and adjacent non-tumor mucosa (N). Equal loading of protein was determined by β-actin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4484478&req=5

Figure 1: The expression of TMEM16A protein in gastric cancer, adjacent and normal tissuesA. A representative hematoxylin and eosin (HE) stained mounted section containing gastric cancer, adjacent and normal gastric mucosa (the upper row, original magnification, ×4) with enlarged view(the middle row, original magnification, ×40). The lower row displayed that TMEM16A was strongly expressed in gastric cancer(the right panel), whereas was moderately or weakly expressed in adjacent(the middle panel) and normal tissues(the left panel) (original magnification, ×40). B. Western blot analysis of TMEM16A protein expression in four pairs of matched gastric tumor (T) and adjacent non-tumor mucosa (N). Equal loading of protein was determined by β-actin.
Mentions: To confirm whether TMEM16A was overexpressed in GC, we performed immunohistochemistry (IHC) of mounted sections, western blotting of surgical samples. Expression of TMEM16A was found to be significantly higher in tumor tissues than that in adjacent non-tumor tissues (Fig. 1A, B). Then, TMEM16A protein expression in 367 GC tissues, corresponding lymph node metastatic lesions and normal gastric tissues was assessed by immunohistochemical staining. Consistent with above result, TMEM16A was strong expressed in GC and lymph node metastasis lesions on tissue microarray (TMA), whereas weak expressed in adjacent non-tumor gastric mucosal tissues.

Bottom Line: A negative correlation between TMEM16A and E-cadherin was found in 367 GC specimens.TMEM16A silencing significantly decreased calcium activated chloride currents, impaired TGF-β secretion, reduced E-cadherin expression, and inhibited the migration and invasion without affecting proliferation of GC cells (AGS and BGC-823).Supplement of TGF-β reverted the effects of TMEM16A silencing on E-cadherin expression, cell migration and invasion.In conclusion, TMEM16A promotes invasion and metastasis in GC, and might be a novel prognostic biomarker and potential therapeutic target in the treatment of GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

ABSTRACT
TMEM16A is a newly identified calcium activated chloride channel, and has been reported to be overexpressed by various solid malignant cancers to promote proliferation and invasion, yet little is known about its role in gastric cancer(GC). Therefore, we investigated the role of TMEM16A in GC and its clinical significance by a retrospective analysis of 367 GC patients, and in vitro study was performed for validation and underlying molecular mechanism.TMEM16A was significantly upregulated and amplified in GC tissues, and its overexpression was positively correlated with disease stage, negatively with patient survival and identified as an independent prognostic factor for patient outcome. A negative correlation between TMEM16A and E-cadherin was found in 367 GC specimens. TMEM16A silencing significantly decreased calcium activated chloride currents, impaired TGF-β secretion, reduced E-cadherin expression, and inhibited the migration and invasion without affecting proliferation of GC cells (AGS and BGC-823). Supplement of TGF-β reverted the effects of TMEM16A silencing on E-cadherin expression, cell migration and invasion.In conclusion, TMEM16A promotes invasion and metastasis in GC, and might be a novel prognostic biomarker and potential therapeutic target in the treatment of GC.

No MeSH data available.


Related in: MedlinePlus