Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UID6 (Kruppel-like)
 147 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kruppel-like factor 6 (KLF6/Zf9/CPBP), a member of the Kruppel-like family of zinc finger transcription factors, has recently been suggested to be a mutated tumor suppressor in selected human cancers. Initially, we investigated whether the KLF6 gene was altered in 36 paired non-small cell lung cancers (NSCLC), 89 brain tumors, 7 normal brains, 46 cancer cell lines from a large variety of tissues, and 144 peripheral blood cells from healthy individuals using single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. Changes in the coding region of KLF6 were found in brain tumors (missense changes, 8%; silent polymorphisms, 2%), lung cancers (missense changes, 3%; silent polymorphisms, 6%) and cancer cell lines (missense changes, 2%; silent polymorphisms, 2%). All of the nucleotide changes in the lung tumor samples were present in their matched normal samples, suggesting that these changes were germline polymorphism. Many of the altered KLF6 genes found in the brain tumors were cloned into an expression vector and placed into a GBM cell line, and cell growth was monitored. Wild-type, deleted exon 3, or E30G missense KLF6 significantly reduced cell growth; in contrast, forced expression of KLF6 having either the S92R, P183L or A276G missense substitution did not alter the growth of transfected GBM cells (p > 0.05). Expression levels of KLF6 were higher in normal brain samples than in glioma samples as measured by real-time RT-PCR (p < 0.05). To our surprise, nucleotide changes were found at -4, -5, and -6 upstream of the start of translation in 45% of brain tumors, and 10% of normal blood samples. Focusing on the most frequent alteration (-4 C > A), the nucleotide change did not affect translation of KLF6. Taking together, KLF6 coding sequences are altered in 10% brain tumors, 8% NSLC, and 4% of cancer cell lines. All of those observed in lung cancer are germline polymorphisms. Several additional ones identified in GBM, have lost their ability to slow the growth of glioma cells; furthermore, a proportion of GBM have decreased expression of KLF6 as compared to normal brain tissue. Dysfunction of this gene may contribute to oncogenesis in the brain.
 ...
PMID:KLF6: mutational analysis and effect on cancer cell proliferation. 1714 13

Phorbol 12-myristate 13-acetate (PMA) modulates cell proliferation and survival by activating several intracellular signaling pathways. Protein kinase C (PKC) plays a key role in PMA-induced growth arrest of non-small cell lung cancer (NSCLC) cells. Kruppel-like transcription factor 6 (KLF6), which is associated with negative control of cell proliferation, is downregulated in many cancers, including NSCLC. In this study, we found that KLF6 is downregulated in 17 lung cancer cell lines and in cells representing early stages of lung cancer development. Moreover, PMA induced cell growth arrest through KLF6 induction in H358 NSCLC cells. The increase in KLF6 by PMA was associated with upregulation of the cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/CIP1) and p27(KIP1). In addition, inhibition of PKC or JNK activation decreased PMA-induced KLF6 induction and activation of PKC alone by Bryostatin-1 and Thymeleatoxin increased KLF6 levels. Moreover, siRNA-mediated knockdown of KLF6 reduced PMA-induced cell growth inhibition concomitantly with decreased expression of both p21(WAF1/CIP1) and p27(KIP1), and in accordance, overexpression of KLF6 alone upregulated both CDKIs protein levels. Our results demonstrate the induction of the tumor suppressor KLF6 following PKC activation and its importance for PMA-mediated cancer cell growth arrest.
 ...
PMID:Activation of protein kinase C by phorbol 12-myristate 13-acetate suppresses the growth of lung cancer cells through KLF6 induction. 1933 10

Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell adhesion. Knockdown of KLF12 in parental cells results in decreased apoptosis following cell detachment from matrix. KLF12 regulates anoikis by promoting the cell cycle transition through S phase and therefore cell proliferation. Reduced expression levels of KLF12 results in increased ability of lung cancer cells to form tumours in vivo and is associated with poorer survival in lung cancer patients. We therefore identify KLF12 as a novel metastasis-suppressor gene whose loss of function is associated with anoikis resistance through control of the cell cycle.
 ...
PMID:Tumour-suppression function of KLF12 through regulation of anoikis. 2645 20