Mutations in the
TWIST1 gene are associated with
Saethre–Chotzen syndrome,
breast cancer, and
Sézary syndrome.
Craniosynostosis TWIST1 mutations are involved in a number of
craniosynostosis presentations. It can present in nonsyndromic forms (isolated
scaphocephaly, right
unicoronal synostosis, and
turricephaly), but also in syndromic forms such as: • Acrocephalosyndactyly type 1 (
Apert syndrome) (primary
FGFR2) •
Beare-Stevenson cutis gyrata syndrome (primary FGFR2) •
Crouzon syndrome (primary FGFR2) •
Crouzon syndrome-acanthosis nigricans syndrome (primary
FGFR3) •
Jackson-Weiss syndrome (primary
FGFR1 or FGFR2) •
Muenke syndrome (primary FGFR3) •
Pfeiffer syndrome (primary FGFR1 or FGFR2)
As an oncogene Twist plays an essential role in cancer metastasis. Over-expression of Twist or
methylation of its
promoter is common in
metastatic carcinomas. Hence targeting Twist has a great promise as a cancer therapeutic. In cooperation with
N-Myc, Twist-1 acts as an
oncogene in several cancers including
neuroblastoma. Twist is activated by a variety of
signal transduction pathways, including
Akt, signal transducer and activator of transcription 3 (
STAT3), mitogen-activated protein kinase,
Ras, and
Wnt signaling. Activated Twist upregulates
N-cadherin and downregulates
E-cadherin, which are the hallmarks of
EMT. Moreover, Twist plays an important role in some physiological processes involved in metastasis, like angiogenesis, invadopodia, extravasation, and chromosomal instability. Twist also protects cancer cells from apoptotic cell death. In addition, Twist is responsible for the maintenance of cancer stem cells and the development of chemotherapy resistance. Twist1 is extensively studied for its role in head- and neck cancers. Here and in epithelial ovarian cancer, Twist1 has been shown to be involved in evading apoptosis, making the tumour cells resistant against platinum-based chemotherapeutic drugs like cisplatin. Moreover, Twist1 has been shown to be expressed under conditions of hypoxia, corresponding to the observation that hypoxic cells respond less to chemotherapeutic drugs. and inhibition of
TIMP. Recently, targeting Twist has gained interest as a target for cancer therapeutics. The inactivation of Twist by
small interfering RNA or
chemotherapeutic approach has been demonstrated
in vitro. Moreover, several inhibitors which are antagonistic to the upstream or downstream molecules of Twist signaling pathways have also been identified. == Interactions ==