Implications of cytokeratin 8/18 filament formation in stratified epithelial cells: Induction of transformed phenotype

Raul, Ujwala; Sawant, Sharada; Dange, Prerana; Kalraiya, Rajiv D.; Ingle, Arvind; Vaidya, Milind M.

doi:10.1002/ijc.20349

Cited by 78 publications

(73 citation statements)

References 31 publications

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“…and S.N.D., unpublished results). These observations are in agreement with earlier reports (Casanova et al, 2004;Raul et al, 2004) and suggest that the K8 and K18 pair contributes to the tumorigenicity of the OSCC cells.…”

Section: Discussionsupporting

confidence: 94%

“…Aberrant expression of this keratin pair at the invasive front of OSCC has also been correlated with invasion of these tumours (Schaafsma et al, 1993). Previously, we have demonstrated that K8 overexpression, and its filament formation with K18, induces neoplastic transformation of the stratified epithelial cell line derived from human foetal buccal mucosa (Raul et al, 2004). These findings were further supported by transgenic studies (Casanova et al, 2004).…”

Section: Discussionmentioning

confidence: 72%

“…Western blotting and immunofluorescence staining was performed as described previously (Raul et al, 2004). The mean fluorescence intensity was measured in arbitrary units using LSM10 software.…”

Section: Keratin Extraction Western Blotting and Immunofluorescence mentioning

confidence: 99%

“…Our previous data has shown that K8 overexpression leads to neoplastic transformation and increased invasive and metastatic potential in the FBM cell line derived from the buccal mucosa of normal human foetus (Raul et al, 2004). Transgenic mice expressing human K8 in the epidermis have a dramatic increase in the progression of papillomas towards malignancy (Casanova et al, 2004).…”

mentioning

confidence: 99%

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Loss of keratins 8 and 18 leads to alterations in α6β4-integrin-mediated signalling and decreased neoplastic progression in an oral-tumour-derived cell line

Alam

Kundu

Dalal

et al. 2011

Journal of Cell Science

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Keratins 8 and 18 (K8 and K18) are predominantly expressed in simple epithelial tissues and perform both mechanical and regulatory functions. Aberrant expression of K8 and K18 is associated with neoplastic progression and invasion in squamous cell carcinomas (SCCs). To understand the molecular basis by which K8 promotes neoplastic progression in oral SCC (OSCC), K8 expression was inhibited in AW13516 cells. The K8-knockdown clones showed a significant reduction in tumorigenic potential, which was accompanied by a reduction in cell motility, cell invasion, decreased fascin levels, alterations in the organization of the actin cytoskeleton and changes in cell shape. Furthermore, K8 knockdown led to a decrease in α6β4 integrin levels and α6β4-integrin-dependent signalling events, which have been reported to play an important role in neoplastic progression in epithelial tissues. Therefore, modulation of α6β4 integrin signalling might be one of the mechanisms by which K8 and K18 promote malignant transformation and/or progression in OSCCs.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 72%

Section: Keratin Extraction Western Blotting and Immunofluorescence mentioning

confidence: 99%

mentioning

confidence: 99%

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Loss of keratins 8 and 18 leads to alterations in α6β4-integrin-mediated signalling and decreased neoplastic progression in an oral-tumour-derived cell line

Alam

Kundu

Dalal

et al. 2011

Journal of Cell Science

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“…Recent studies could show that this cytokeratin pair seems to play an important role in the pathogenesis and progression of OSCCs. The transfection of buccal mucosa cells with a vector for Ck 8/18 resulted in a significantly altered cellular morphology and increased cell motilityfeatures associated with or being prerequisites for invasive tumour behaviour (20). This was in line with previous experiments in melanoma cells (21).…”

Section: Discussionsupporting

confidence: 89%

Cytokeratin alteration in oral leukoplakia and oral squamous cell carcinoma

Fillies

Jogschies²,

Kleinheinz³

et al. 2007

Oncol Rep

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Generation of a tissue‐specific transgenic model for K8 phosphomutants: A tool to investigate the role of K8 phosphorylation during skin carcinogenesis in vivo

Tiwari

Ganguli

Alam

et al. 2021

Cell Biology International

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Keratin 8/18, the predominant keratin pair of simple epithelia, is known to be aberrantly expressed in several squamous cell carcinomas (SCCs), where its expression is often correlated with increased invasion, neoplastic progression, and poor prognosis. The majority of keratin 8/18 structural and regulatory functions are governed by posttranslational modifications, particularly phosphorylation. Apart from filament reorganization, cellular processes including cell cycle, cell growth, cellular stress, and apoptosis are known to be orchestrated by K8 phosphorylation at specific residues in the head and tail domains. Even though deregulation of K8 phosphorylation at two significant sites (Serine 73 /Serine 431 ) has been implicated in neoplastic progression of SCCs by various in vitro studies, including ours, it is reported to be highly context-dependent. Therefore, to delineate the precise role of Kereatin 8 phosphorylation in cancer initiation and progression, we have developed the tissue-specific transgenic mouse model expressing Keratin 8 wild type and phosphodead mutants under Keratin 14 promoter. Subjecting these mice to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-mediated skin carcinogenesis revealed that Keratin 8 phosphorylation may lead to an early onset of tumors compared to Keratin 8 wild-type expressing mice. Conclusively, the transgenic mouse model developed in the present study ascertained a positive impact of Keratin 8 phosphorylation on the neoplastic transformation of skinsquamous cells.

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Implications of cytokeratin 8/18 filament formation in stratified epithelial cells: Induction of transformed phenotype

Cited by 78 publications

References 31 publications

Loss of keratins 8 and 18 leads to alterations in α6β4-integrin-mediated signalling and decreased neoplastic progression in an oral-tumour-derived cell line

Loss of keratins 8 and 18 leads to alterations in α6β4-integrin-mediated signalling and decreased neoplastic progression in an oral-tumour-derived cell line

Cytokeratin alteration in oral leukoplakia and oral squamous cell carcinoma

Generation of a tissue‐specific transgenic model for K8 phosphomutants: A tool to investigate the role of K8 phosphorylation during skin carcinogenesis in vivo

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