Journal Article

STAT3 induces anoikis resistance, promotes cell invasion and metastatic potential in pancreatic cancer cells

Neel M. Fofaria and Sanjay K. Srivastava

in Carcinogenesis

Volume 36, issue 1, pages 142-150
Published in print January 2015 | ISSN: 0143-3334
Published online November 2014 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgu233
STAT3 induces anoikis resistance, promotes cell invasion and metastatic potential in pancreatic cancer cells

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Tumor cells need to attain anoikis resistance to survive prior to metastasis making it a vital trait of malignancy. The mechanism by which pancreatic cancer cells resist anoikis and metastasize is not well established. Significant proportion of pancreatic cancer cells resisted anoikis when grown under anchorage-independent conditions. The cells that resisted anoikis showed higher migratory and invasive characteristics than the cells that were cultured under anchorage-dependent condition. Interestingly, anoikis-resistant cells exhibited significantly increased expression and phosphorylation of signal transducer and activation of transcription 3 (STAT3) at Tyr 705, as compared to adherent cells. AG 490 and piplartine (PL) induced significant anoikis in anoikis-resistant pancreatic cancer cells. Silencing STAT3 not only reduced the capacity of pancreatic cancer cells to resist anoikis but also reversed its invasive characteristics. Interleukin-6 treatment and overexpression of STAT3 enhanced anoikis resistance and protected the cells from PL-induced anoikis. PL-treated cells completely failed to develop tumors when injected subcutaneously in immune-compromised mice. Moreover, these cells also failed to metastasize when injected intravenously. On the other hand, untreated anoikis-resistant cells not only formed aggressive tumors but also metastasized substantially to lungs and liver when injected intravenously. Metastatic nodules formed by untreated anoikis-resistant cells in lungs exhibited significant phosphorylation of STAT3 at Tyr705. Taken together, our results established the critical involvement of STAT3 in conferring anoikis resistance to pancreatic cancer cells and increased metastasis.

Journal Article.  6585 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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